Condensin

{{Short description|Protein complex}} 450px|thumb|Figure 1. An interphase nucleus (left) and a set of mitotic chromosomes (right) from human tissue culture cells. Bar, 10 μm. '''Condensins''' are large protein complexes that play a central role in chromosome condensation and segregation during mitosis and meiosis (Figure 1).<ref name="pmid26919425">{{cite journal |vauthors=Hirano T | title = Condensin-based chromosome organization from bacteria to vertebrates | journal = Cell | volume = 164 | issue = 5 | pages =847–857 | year = 2016| pmid =26919425 | doi=10.1016/j.cell.2016.01.033| doi-access = free }}</ref><ref>{{cite journal |vauthors=Kalitsis P, Zhang T, Marshall KM, Nielsen CF, Hudson DF | title = Condensin, master organizer of the genome | journal = Chromosome Res. | volume = 25 | issue = 1 |pages = 61–76 | year = 2017 | doi = 10.1007/s10577-017-9553-0 | pmid = 28181049 | s2cid = 28241964 }}</ref> Their subunits were originally identified as major components of mitotic chromosomes assembled in ''Xenopus'' egg extracts.<ref name="pmid9160743"/>

== Subunit composition and phylogeny ==

=== Eukaryotic types === 400px|thumb|Figure 2. Three eukaryotic condensin complexes Many eukaryotic cells possess two different types of condensin complexes, known as '''condensin I''' and '''condensin II''', each of which is composed of five subunits (Figure 2).<ref name="pmid9160743">{{cite journal | vauthors = Hirano T, Kobayashi R, Hirano M | title = Condensins, chromosome condensation complex containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein | journal = Cell | volume = 89 | issue = 4 | pages = 511–21 | year = 1997 | pmid = 9160743 | doi=10.1016/S0092-8674(00)80233-0| s2cid = 15061740 | doi-access = free}}</ref><ref name="pmid14532007">{{cite journal | vauthors = Ono T, Losada A, Hirano M, Myers MP, Neuwald AF, Hirano T | title = Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells | journal = Cell| volume = 115 | issue = 1 | pages = 109–21 | year = 2003 | doi = 10.1016/s0092-8674(03)00724-4 | pmid = 14532007| s2cid = 18811084 | doi-access = free }}</ref> Condensins I and II share the same pair of core subunits, SMC2 and SMC4, both belonging to a large family of chromosomal ATPases, known as '''SMC''' proteins (SMC stands for Structural Maintenance of Chromosomes).<ref name="pmid27075410">{{cite journal |vauthors=Uhlmann F | title = SMC complexes: from DNA to chromosomes| journal = Nat. Rev. Mol. Cell Biol. | volume = 17 | issue = 7| pages = 399–412 | year = 2016 | pmid = 27075410 | doi=10.1038/nrm.2016.30| s2cid = 20398243| url = https://figshare.com/articles/journal_contribution/25913146}}</ref><ref name="pmid31577909">{{cite journal |vauthors=Yatskevich S, Rhodes J, Nasmyth K | title = Organization of chromosomal DNA by SMC complexes| journal = Annu. Rev. Genet. | volume = 53 | pages =445–482| year = 2019 | doi = 10.1146/annurev-genet-112618-043633| pmid = 31577909| doi-access =free }}</ref> Each of the complexes contains a distinct set of non-SMC regulatory subunits (a '''kleisin''' subunit<ref name="pmid12667442">{{cite journal | vauthors = Schleiffer A, Kaitna S, Maurer-Stroh S, Glotzer M, Nasmyth K, Eisenhaber F | title = Kleisins: a superfamily of bacterial and eukaryotic SMC protein partners | journal = Mol. Cell| volume = 11 | issue = 3 | pages = 571–5 | year = 2003 | pmid = 12667442 | doi=10.1016/S1097-2765(03)00108-4| doi-access = free }}</ref> and a pair of '''HEAT repeat''' subunits).<ref name="pmid11042144">{{cite journal | vauthors = Neuwald AF, Hirano T | title = HEAT repeats associated with condensins, cohesins, and other complexes involved in chromosome-related functions | journal = Genome Res.| volume = 10 | issue = 10 | pages = 1445–52 | year = 2000 | pmid = 11042144 | doi=10.1101/gr.147400 | pmc=310966}}</ref> Both complexes are large, having a total molecular mass of 650-700 kDa.

The core subunits condensins (SMC2 and SMC4) are conserved among all eukaryotic species that have been studied to date. The non-SMC subunits unique to condensin I are also conserved among eukaryotes, but the occurrence of the non-SMC subunits unique to condensin II is highly variable among species.

*For instance, the fruit fly ''Drosophila melanogaster'' does not have the gene for the CAP-G2 subunit of condensin II.<ref name="pmid23637630">{{cite journal | vauthors = Herzog S, Nagarkar Jaiswal S, Urban E, Riemer A, Fischer S, Heidmann SK | title =Functional dissection of the Drosophila melanogaster condensin subunit Cap-G reveals its exclusive association with condensin I | journal = PLOS Genet.| volume = 9 | issue = 4 | article-number = e1003463 | year = 2013| doi =10.1371/journal.pgen.1003463 | pmid = 23637630| pmc =3630105 | doi-access =free }}</ref> Other insect species often lack the genes for the CAP-D3 and/or CAP-H subunits, too, indicating that the non-SMC subunits unique to condensin II have been under high selection pressure during insect evolution.<ref name="pmid31270536">{{cite journal |last1=King |first1=Thomas D |last2=Leonard |first2=Christopher J |last3=Cooper |first3=Jacob C |last4=Nguyen |first4=Son |last5=Joyce |first5=Eric F |last6=Phadnis |first6=Nitin |last7=Takahashi |first7=Aya |title=Recurrent Losses and Rapid Evolution of the Condensin II Complex in Insects |journal=Molecular Biology and Evolution |date=October 2019 |volume=36 |issue=10 |pages=2195–2204 |doi=10.1093/molbev/msz140 |pmid=31270536 |pmc=6759200 }}</ref> *The nematode ''Caenorhabditis elegans'' possesses both condensins I and II. This species is, however, unique in the sense that it has a third complex (closely related to condensin I) that participates in chromosome-wide gene regulation, i.e., dosage compensation.<ref name="pmid19119011">{{cite journal | vauthors = Csankovszki G, Collette K, Spahl K, Carey J, Snyder M, Petty E, Patel U, Tabuchi T, Liu H, McLeod I, Thompson J, Sarkeshik A, Yates J, Meyer BJ, Hagstrom K | title = Three distinct condensin complexes control C. elegans chromosome dynamics | journal = Curr. Biol. | volume = 19 | issue = 1 | pages = 9–19 | year = 2009 | pmid = 19119011 | doi=10.1016/j.cub.2008.12.006 | pmc=2682549| bibcode = 2009CBio...19....9C }}</ref> In this complex, known as condensin I^DC, the authentic SMC4 subunit is replaced with its variant, DPY-27 (Figure 2). Furthermore, in this organism, condensin I appears to play a role in interphase chromosome organization that is functionally analogous to that of cohesin in vertebrates.<ref name="pmid39039278">{{cite journal |vauthors=Das M, Semple JI, Haemmerli A, Volodkina V, Scotton J, Gitchev T, Annan A, Campos J, Statzer C, Dakhovnik A, Ewald CY, Mozziconacci J, Meister P | title = Condensin I folds the Caenorhabditis elegans genome | journal = Nat. Genet. | volume = 56 | issue = 8| pages = 1737–1749| year = 2024 | doi = 10.1038/s41588-024-01832-5 | pmid = 39039278}}</ref> *Some species, like fungi (e.g., the budding yeast ''Saccharomyces cerevisiae'' and the fission yeast ''Schizosaccharomyces pombe''), lack all regulatory subunits unique to condensin II.<ref name="pmid10485849">{{cite journal | vauthors = Sutani T, Yuasa T, Tomonaga T, Dohmae N, Takio K, Yanagida M | title = Fission yeast condensin complex: essential roles of non-SMC subunits for condensation and Cdc2 phosphorylation of Cut3/SMC4 | journal = Genes Dev.| volume = 13 | issue = 17 | pages = 2271–83 | year = 1999 | doi = 10.1101/gad.13.17.2271 | pmid = 10485849| pmc = 316991 }}</ref><ref name="pmid10811823">{{cite journal | vauthors = Freeman L, Aragon-Alcaide L, Strunnikov A | title = The condensin complex governs chromosome condensation and mitotic transmission of rDNA | journal = J. Cell Biol. | volume = 149 | issue = 4 | pages = 811–824 | year = 2000 | pmid = 10811823 | doi=10.1083/jcb.149.4.811 | pmc=2174567}}</ref> On the other hand, the unicellular, primitive red alga ''Cyanidioschyzon merolae'', whose genome size is comparable to those of the yeast, has both condensins I and II.<ref name="pmid23783031">{{cite journal | vauthors = Fujiwara T, Tanaka K, Kuroiwa T, Hirano T | title = Spatiotemporal dynamics of condensins I and II: evolutionary insights from the primitive red alga Cyanidioschyzon merolae | journal = Mol. Biol. Cell | volume = 24 | issue = 16 | pages = 2515–27 | year = 2013 | doi = 10.1091/mbc.E13-04-0208 | pmid = 23783031| pmc = 3744952 }}</ref> Thus, there is no apparent relationship between the occurrence of condensin II and the size of eukaryotic genomes. *''Arabidopsis thaliana'' possesses two SMC2 paralogs, CAP-E1 and CAP-E2.<ref name="pmid12783798">{{cite journal |vauthors=Siddiqui NU, Stronghill PE, Dengler RE, Hasenkampf CA, Riggs CD | title = Mutations in Arabidopsis condensin genes disrupt embryogenesis, meristem organization and segregation of homologous chromosomes during meiosis | journal = Development | volume = 130 | issue = 14 | pages = 3283–3295 | year = 2003 | pmid = 12783798 | doi = 10.1242/dev.00542}}</ref> While mutations in either gene alone do not significantly impair development, the double mutant is embryonic lethal. *The ciliate ''Tetrahymena thermophila'' has condensin I only. Nevertheless, there are multiple paralogs for two of its regulatory subunits (CAP-D2 and CAP-H), and some of them specifically localize to either the macronucleus (responsible for gene expression) or the micronucleus (responsible for reproduction).<ref name="pmid29237819">{{cite journal | vauthors = Howard-Till R, Loidl J | title =Condensins promote chromosome individualization and segregation during mitosis, meiosis, and amitosis in Tetrahymena thermophila | journal = Mol. Biol. Cell| volume = 29 | issue = 4 | pages = 466–478 | year = 2018| doi =10.1091/mbc.E17-07-0451 | pmid = 29237819| pmc =6014175 }}</ref> Thus, this species has multiple condensin I complexes that have different regulatory subunits and display distinct nuclear localization.<ref name="pmid30893010">{{cite journal |last1=Howard-Till |first1=Rachel |last2=Tian |first2=Miao |last3=Loidl |first3=Josef |last4=Cohen-Fix |first4=Orna |title=A specialized condensin complex participates in somatic nuclear maturation in |journal=Molecular Biology of the Cell |date=15 May 2019 |volume=30 |issue=11 |pages=1326–38 |doi=10.1091/mbc.E18-08-0487 |pmid=30893010 |pmc=6724606 }}</ref> This is a very unique property that is not found in other species.

The following table summarizes the names of SMC complex subunits in representative eukaryotic model organisms.

{| class="wikitable" |- ! Complex !! Subunit !! Vertebrate !! ''D. melanogaster'' !! ''C. elegans'' !! ''S. cerevisiae'' !! ''S. pombe'' !! ''A. thaliana''!!''T. thermophila'' |- ! rowspan="2" | condensin I & II | SMC2 ATPase || CAP-E/ SMC2 || Smc2 || MIX-1 || Smc2 || Cut14 || CAP-E1 & -E2 || Smc2 |- | SMC4 ATPase || CAP-C/ SMC4 || Smc4/ Gluon || SMC-4 || Smc4 || Cut3 || CAP-C || Smc4 |- ! rowspan="3" | condensin I | kleisin || CAP-H || CAP-H/ Barren || DPY-26 || Brn1 || Cnd2 || CAP-H || Cph1,2,3,4 & 5 |- | HEAT-IA ||CAP-D2 || CAP-D2 || DPY-28 || Ycs4 || Cnd1 || CAP-D2 || Cpd1 & 2 |- | HEAT-IB || CAP-G || CAP-G || CAPG-1 || Ycg1 || Cnd3 || CAP-G || Cpg1 |- ! rowspan="3" | condensin II | kleisin || CAP-H2 || CAP-H2 || KLE-2 || - || - || CAP-H2/ HEB2 || - |- | HEAT-IIA || CAP-D3 ||CAP-D3 || HCP-6 || - || - || CAP-D3 || - |- | HEAT-IIB || CAP-G2 || - || CAP-G2 || - || - || CAP-G2/ HEB1 || - |- ! rowspan="1" | condensin I ^DC | SMC4 variant || - || - || DPY-27 || - || - || - || - |- |}

Condensin is one of the three major SMC protein complexes found in eukaryotes. The other two are: '''cohesin''', which is involved in sister chromatid cohesion and interphase chromosome organization; and '''the SMC5/6 complex''', which functions in DNA repair and chromosome segregation.<ref name="pmid27075410"/><ref name="pmid31577909"/>

===Prokaryotic types=== 500px|thumb|Figure 3. Prokaryotic condensin-like complexes '''SMC-ScpAB''': Condensin-like protein complexes also exist in prokaryotes, where they contribute to the organization and segregation of chromosomes (nucleoids). The best-studied example is the SMC–ScpAB complex (Figure 3, left),<ref name="pmid12065423">{{cite journal |vauthors=Mascarenhas J, Soppa J, Strunnikov AV, Graumann PL | title = Cell cycle-dependent localization of two novel prokaryotic chromosome segregation and condensation proteins in Bacillus subtilis that interact with SMC protein | journal = EMBO J.| volume = 21 | issue = 12 | pages = 3108–18 | year = 2002 | doi = 10.1093/emboj/cdf314 | pmid = 12065423| pmc = 126067 }}</ref> which is considered the evolutionary ancestor of the eukaryotic condensin complexes. Compared to its eukaryotic counterparts, SMC–ScpAB has a simpler architecture. For instance, while eukaryotic condensins contain an SMC heterodimer, prokaryotic SMC proteins form a homodimer. Among the regulatory subunits, ScpA belongs to the kleisin family,<ref name="pmid12667442" /> suggesting that the basic SMC–kleisin trimeric structure is conserved across prokaryotes and eukaryotes. By contrast, ScpB is classified as a member of the kite (Kleisin Interacting Tandem Elements) family,<ref name="pmid26585514">{{cite journal |vauthors=Palecek JJ, Gruber S | title = Kite proteins: a superfamily of SMC/kleisin partners conserved across Bacteria, Archaea, and Eukaryotes | journal = Structure| volume = 23 | issue = 12 | pages = 2183–2190 | year = 2015 | doi = 10.1016/j.str.2015.10.004 | pmid = 26585514| doi-access = free }}</ref> which is structurally distinct from the HEAT-repeat subunits found in eukaryotic condensins.<ref name="pmid11042144" /><ref name="pmid 27802131">{{cite journal |vauthors=Yoshimura SH, Hirano T | title = HEAT repeats - versatile arrays of amphiphilic helices working in crowded environments? | journal = J. Cell Sci. | volume = 129 | issue = 21| pages = 3963–3970 | year = 2016 | doi = 10.1242/jcs.185710 | pmid = 27802131}}</ref>

'''MukBEF''': While most bacteria and archaea possess the SMC–ScpAB complex, a subset of gammaproteobacteria, including ''Escherichia coli'', instead have a distinct SMC complex known as MukBEF.<ref name="pmid10545099">{{cite journal |vauthors=Yamazoe M, Onogi T, Sunako Y, Niki H, Yamanaka K, Ichimura T, Hiraga S | title = Complex formation of MukB, MukE and MukF proteins involved in chromosome partitioning in Escherichia coli | journal = EMBO J.| volume = 18 | issue = 21 | pages = 5873–84 | year = 1999 | doi = 10.1093/emboj/18.21.5873 | pmid = 10545099| pmc = 1171653 }}</ref> MukBEF forms a "dimer-of-dimers" through dimerization mediated by the kleisin subunit MukF (Figure 3, center). The third subunit, MukE, belongs to the kite family. Although sequence similarity between the subunits of MukBEF and those of SMC–ScpAB is low, their overall molecular architecture observed by electron microscopy<ref name="pmid9744887" /> and phenotypic defects in mutants<ref name="pmid1989883">{{cite journal |vauthors=Niki H, Jaffé A, Imamura R, Ogura T, Hiraga S| title = The new gene mukB codes for a 177 kd protein with coiled-coil domains involved in chromosome partitioning of E. coli| journal = EMBO J.| volume = 10 | issue = 1 | pages = 183–193| year = 1991 | doi = 10.1002/j.1460-2075.1991.tb07935.x| pmid = 1989883| pmc = 452628}}</ref><ref name="pmid9573042">{{cite journal |vauthors=Britton RA, Lin DC, Grossman AD | title = Characterization of a prokaryotic SMC protein involved in chromosome partitioning | journal = Genes Dev | volume = 12 | issue = 9 | pages = 1254–1259 | year = 1998 | pmid = 9573042 | doi = 10.1101/gad.12.9.1254| pmc = 316777 }}</ref> suggest that the two are functional homologs. As such, they are often collectively referred to as prokaryotic condensins.

'''MksBEF'''/'''Wadjet''': More recently, a third type of bacterial SMC complex (called MksBEF), structurally similar to MukBEF, has been reported.<ref name="pmid21752107">{{cite journal |vauthors=Petrushenko ZM, She W, Rybenkov VV | title = A new family of bacterial condensins | journal = Mol. Microbiol.| volume = 81 | issue = 4 | pages = 881–896 | year = 2011 | doi = 10.1111/j.1365-2958.2011.07763.x | pmid = 21752107| pmc = 3179180 }}</ref> ''Pseudomonas aeruginosa'' have both SMC–ScpAB and MksBEF, which contribute to chromosome organization and segregation through distinct mechanisms.<ref name="pmid33147461">{{cite journal |vauthors=Lioy VS, Junier I, Lagage V, Vallet I, Boccard F | title = Distinct Activities of Bacterial Condensins for Chromosome Management in Pseudomonas aeruginosa | journal = Cell Rep | volume = 33 | issue = 5 | article-number = 108344 | year = 2020 | doi = 10.1016/j.celrep.2020.108344 | pmid =33147461| doi-access = free }}</ref> In contrast, in ''Corynebacterium glutamicum'', SMC–ScpAB is responsible for chromosome architecture and segregation, whereas MksBEF, together with the nuclease subunit MksG, is specialized for plasmid defense.<ref name="pmid32198399">{{cite journal |vauthors=Böhm K, Giacomelli G, Schmidt A, Imhof A, Koszul R, Marbouty M, Bramkamp M | title = Chromosome organization by a conserved condensin-ParB system in the actinobacterium Corynebacterium glutamicum | journal = Nat Commun | volume = 11 | issue = 1 | page = 1485 | year = 2020 | doi = 10.1038/s41467-020-15238-4 | pmid =32198399| pmc = 7083940 | bibcode = 2020NatCo..11.1485B }}</ref><ref name="pmid36881760">{{cite journal |vauthors=Weiß M, Giacomelli G, Assaya MB, Grundt F, Haouz A, Peng F, Petrella S, Wehenkel AM, Bramkamp M | title = The MksG nuclease is the executing part of the bacterial plasmid defense system MksBEFG | journal = Nucl Acids Res| volume = 51 | issue = 7 | pages = 3288–3306 | year = 2023 | doi = 10.1093/nar/gkad130 | pmid =36881760| pmc = 10123090 }}</ref> The MksBEFG complex is orthologous to the JetABCD complex in ''Bacillus cereus''<ref name="pmid36206765">{{cite journal |vauthors=Deep A, Gu Y, Gao YQ, Ego KM, Herzik MA Jr, Zhou H, Corbett KD | title = The SMC-family Wadjet complex protects bacteria from plasmid transformation by recognition and cleavage of closed-circular DNA | journal = Mol Cell | volume = 82 | issue = 21 | pages = 4145–4159.e7 | year = 2022 | doi = 10.1016/j.molcel.2022.09.008 | pmid =36206765| pmc = 9637719 }}</ref><ref name="pmid36525956">{{cite journal |vauthors=Liu HW, Roisné-Hamelin F, Beckert B, Li Y, Myasnikov A, Gruber S | title = DNA-measuring Wadjet SMC ATPases restrict smaller circular plasmids by DNA cleavage | journal = Mol Cell | volume = 82 | issue = 24 | pages = 4727–4740.e6 | year = 2022 | doi = 10.1016/j.molcel.2022.11.015 | pmid =36525956| doi-access = free }}</ref> and the EptABCD complex in ''Mycobacterium smegmatis''.<ref name="pmid25197070">{{cite journal |vauthors=Panas MW, Jain P, Yang H, Mitra S, Biswas D, Wattam AR, Letvin NL, Jacobs WR Jr | title = Noncanonical SMC protein in Mycobacterium smegmatis restricts maintenance of Mycobacterium fortuitum plasmids | journal = Proc Natl Acad Sci USA | volume = 111 | issue = 37 | pages = 13264–13271 | year = 2014 | doi = 10.1073/pnas.1414207111 | doi-access = free | pmid =25197070| pmc = 4169951 | bibcode = 2014PNAS..11113264P }}</ref> These complexes, which serve a common function in plasmid defense, are collectively referred to as the Wadjet complexes (Figure 3, right).

The following table summarizes the names of SMC complex subunits in representative prokaryotic model organisms.

{| class="wikitable" |- ! Complex !! Subunit !! ''B. subtilis'' !! ''C. crescentus'' !! ''E. coli'' !! ''P. aeruginosa''!!''C. glutamicum'' !! ''B. cereus'' |- ! rowspan="3" | SMC-ScpAB | SMC ATPase || SMC || SMC || - || SMC || SMC || SMC |- | kleisin || ScpA || ScpA || - || ScpA|| ScpA|| ScpA |- | kite || ScpB || ScpB || - || ScpB|| ScpB|| ScpB |- ! rowspan="3" | MukBEF | SMC ATPase || - || - || MukB || -|| -|| - |- | kleisin || - || - || MukF || -|| -|| - |- | kite || - || - || MukE || -|| -|| - |- ! rowspan="4" | MksBEF & Wadjet | SMC ATPase || - || - || - || MksB || MksB|| JetC |- | kleisin || - || - || - || MksF || MksF|| JetA |- | kite || - || - || - || MksE || MksE|| JetB |- | nuclease || - || - || - || - || MksG|| JetD |- |}

==Molecular structures== 400px|thumb|Figure 4. Basic structure of a condensin complex SMC dimers that act as the core subunits of condensins display a highly characteristic V-shape, each arm of which is composed of anti-parallel coiled-coils (Figure 4; see SMC proteins for details).<ref name="pmid9744887">{{cite journal | vauthors = Melby TE, Ciampaglio CN, Briscoe G, Erickson HP| title = The symmetrical structure of structural maintenance of chromosomes (SMC) and MukB proteins: long, antiparallel coiled coils, folded at a flexible hinge| journal = J. Cell Biol.| volume = 142 | issue = 6 | pages = 1595–1604 | year = 1998 | pmid = 9744887 | doi=10.1083/jcb.142.6.1595 | pmc=2141774}}</ref><ref name="pmid11815634">{{cite journal | vauthors = Anderson DE, Losada A, Erickson HP, Hirano T| title = Condensin and cohesin display different arm conformations with characteristic hinge angles| journal = J. Cell Biol.| volume = 156 | issue = 6 | pages = 419–424 | year = 2002 | pmid = 11815634 | doi=10.1083/jcb.200111002 | pmc=2173330}}</ref> The length of each coiled-coil arm reaches ~50&nbsp;nm, which corresponds to the length of ~150 bp of double-stranded DNA (dsDNA). On the other hand, fast-speed atomic force microscopy has demonstrated that the arms of an SMC dimer is far more flexible than was expected.<ref name="pmid26904946">{{cite journal | vauthors = Eeftens JM, Katan AJ, Kschonsak M, Hassler M, de Wilde L, Dief EM, Haering CH, Dekker C | title =Condensin Smc2-Smc4 dimers are flexible and dynamic | journal = Cell Rep | volume = 14 | issue = 8 | pages = 1813–8 | year = 2016 | doi =10.1016/j.celrep.2016.01.063 | pmid = 26904946| pmc =4785793 }}</ref>

The formation of a condensin or condensin-like complex involves the association of an SMC dimer with non-SMC subunits (Figure 4). First, the N-terminal domain of the kleisin subunit binds to the neck region (a segment of the coiled coil near the head domain) of one SMC protein, while its C-terminal domain binds to the cap region (part of the head domain) of the other SMC subunit. These interactions result in the formation of a asymmetric ring-like architecture. Finally, two HEAT-repeat subunits (or two kite subunits depending on the complex) associate with the central region of the kleisin, completing the assembly of the holo-complex. MukBEF and Wadjet form higher-order assemblies through dimerization mediated by their kleisin subunits, a configuration often referred to as a "dimer-of-dimers" (Figure 3).

Structural information on individual complexes or their subcomplexes has been reported as follows: * Prokaryotic '''SMC-ScpAB''': Early X-ray crystallography studies revealed partial structures of ScpAB<ref name="pmid23353789">{{cite journal | vauthors = Bürmann F, Shin HC, Basquin J, Soh YM, Giménez-Oya V, Kim YG, Oh BH, Gruber S | title = An asymmetric SMC-kleisin bridge in prokaryotic condensin | journal = Nat. Struct. Mol. Biol.| volume = 20 | issue = 3 | pages = 371–9 | year = 2013| doi = 10.1038/nsmb.2488 | pmid = 23353789| s2cid = 21584205 }}</ref><ref name="pmid23541893">{{cite journal | vauthors = Kamada K, Miyata M, Hirano T | title = Molecular basis of SMC ATPase activation: role of internal structural changes of the regulatory subcomplex ScpAB | journal = Structure| volume = 21 | issue = 4 | pages = 581–594 | year = 2013| doi = 10.1016/j.str.2013.02.016 | pmid = 23541893| doi-access = free }}</ref> as well as the interaction interface between SMC and kleisin subunits.<ref name="pmid23353789"/> * Prokaryotic '''MukBEF''': In addition to early X-ray crystallography studies,<ref name="pmid15902272">{{cite journal | vauthors = Fennell-Fezzie R, Gradia SD, Akey D, Berger JM | title =The MukF subunit of Escherichia coli condensin: architecture and functional relationship to kleisins | journal = EMBO J.| volume = 24 | issue = 11 | pages = 1921–30 | year = 2005| doi =10.1038/sj.emboj.7600680 | pmid = 15902272| pmc =1142612 }}</ref><ref name="pmid19135891">{{cite journal | vauthors = Woo JS, Lim JH, Shin HC, Suh MK, Ku B, Lee KH, Joo K, Robinson H, Lee J, Park SY, Ha NC, Oh BH | title = Structural studies of a bacterial condensin complex reveal ATP-dependent disruption of intersubunit interactions | journal = Cell| volume = 136 | issue = 1 | pages = 85–96 | year = 2009| doi = 10.1016/j.cell.2008.10.050 | pmid = 19135891| s2cid = 4608756 | doi-access = free }}</ref> more recent analyses using cryo-EM have visualized the steps of dissociation from DNA<ref name="pmid34739874">{{cite journal |vauthors=Bürmann F, Funke LF, Chin JW, Löwe J | title = Cryo-EM structure of MukBEF reveals DNA loop entrapment at chromosomal unloading sites | journal = Mol Cell | volume = 81 | issue = 23 | pages = 4891–4906.e8 | year = 2021 | pmid = 34739874 | doi = 10.1016/j.molcel.2021.10.011| pmc = 8669397 }}</ref> and of loading onto DNA.<ref name="pmid40168993">{{cite journal |vauthors=Bürmann F, Clifton B, Koekemoer S, Wilkinson OJ, Kimanius D, Dillingham MS, Löwe J | title = Mechanism of DNA capture by the MukBEF SMC complex and its inhibition by a viral DNA mimic | journal = Cell | year = 2025 | volume = 188 | issue = 9 | pages = 2465–2479.e14 | pmid = 40168993 | doi = 10.1016/j.cell.2025.02.032| doi-access = free | pmc = 7617805 }}</ref> * Prokaryotic '''Wadjet''': The structure of the Wadjet complex, involved in plasmid defense, has been resolved by cryo-EM.<ref name="pmid36525956"/><ref name="pmid38309275">{{cite journal |vauthors=Roisné-Hamelin F, Liu HW, Taschner M, Li Y, Gruber S | title = Structural basis for plasmid restriction by SMC JET nuclease | journal = Mol Cell | volume = 84 | issue = 5 | pages = 883–896.e7 | year = 2024 | pmid = 38309275 | doi = 10.1016/j.molcel.2024.01.009| doi-access = free }}</ref> * Eukaryotic '''condensins''': Several structures of subcomplexes and subdomains have been reported, including the hinge<ref name="pmid20139420">{{cite journal | vauthors = Griese JJ, Witte G, Hopfner KP | title = Structure and DNA binding activity of the mouse condensin hinge domain highlight common and diverse features of SMC proteins | journal = Nucleic Acids Res.| volume = 38 | issue = 10 | pages = 3454–65 | year = 2010 | doi = 10.1093/nar/gkq038 | pmid = 20139420| pmc = 2879519 }}</ref> and arm<ref name="pmid25557547">{{cite journal | vauthors = Soh Y, Bürmann F, Shin H, Oda T, Jin KS, Toseland CP, Kim C, Lee H, Kim SJ, Kong M, Durand-Diebold M, Kim Y, Kim HM, Lee NK, Sato M, Oh B, Gruber S | title =Molecular basis for SMC rod formation and its dissolution upon DNA binding | journal = Mol. Cell | volume = 57 | issue = 2 | pages = 290–303 | year = 2015 | doi =10.1016/j.molcel.2014.11.023 | pmid = 25557547| pmc =4306524 }}</ref> domains of an SMC2-SMC4 dimer, a CAP-G(ycg1)/CAP-H(brn1) subcomplex,<ref name="pmid28988770">{{cite journal | vauthors = Kschonsak M, Merkel F, Bisht S, Metz J, Rybin V, Hassler M, Haering CH| title =Structural basis for a safety-belt mechanism that anchors condensin to chromosomes | journal = Cell | volume = 171 | issue = 3 | pages = 588–600.e24 | year = 2017 | doi =10.1016/j.cell.2017.09.008 | pmid =28988770| pmc =5651216 }}</ref><ref name="pmid30858338">{{cite journal |last1=Hara |first1=Kodai |last2=Kinoshita |first2=Kazuhisa |last3=Migita |first3=Tomoko |last4=Murakami |first4=Kei |last5=Shimizu |first5=Kenichiro |last6=Takeuchi |first6=Kozo |last7=Hirano |first7=Tatsuya |last8=Hashimoto |first8=Hiroshi |title=Structural basis of HEAT-kleisin interactions in the human condensin I subcomplex |journal=EMBO Reports |date=12 March 2019 |volume=20 |issue=5 |doi=10.15252/embr.201847183 |pmid=30858338 |pmc=6501013 }}</ref> and a CAP-D2(ycs4)/CAP-H(brn1) subcomplex.<ref name="pmid31226277">{{cite journal |vauthors=Hassler M, Shaltiel IA, Kschonsak M, Simon B, Merkel F, Thärichen L, Bailey HJ, Macošek J, Bravo S, Metz J, Hennig J, Haering CH| title =Structural basis of an asymmetric condensin ATPase cycle | journal = Mol Cell | volume = 74 | issue = 6 | pages = 1175–1188.e24 | year = 2019 | doi =10.1016/j.molcel.2019.03.037 | pmid =31226277| pmc =6591010 }}</ref> More recently, a series of cryo-EM studies has shown that condensin undergoes large conformational changes that are coupled with ATP-binding and hydrolysis by its SMC subunits.<ref name="pmid32661420">{{cite journal | vauthors = Lee BG, Merkel F, Allegretti M, Hassler M, Cawood C, Lecomte L, O'Reilly FJ, Sinn LR, Gutierrez-Escribano P, Kschonsak M, Bravo S, Nakane T, Rappsilber J, Aragon L, Beck M, Löwe J, Haering CH | title = Cryo-EM structures of holo condensin reveal a subunit flip-flop mechanism | journal = Nat Struct Mol Biol | volume = 27 | issue = 8 | pages = 743–751 | year = 2020 | doi = 10.1038/s41594-020-0457-x | pmid = 32661420| pmc = 7610691 }}</ref><ref name="pmid35349345">{{cite journal |vauthors=Lee BG, Rhodes J, Löwe J | title = Clamping of DNA shuts the condensin neck gate | journal = Proc Natl Acad Sci USA | volume = 119 | issue = 14 | article-number = e2120006119 | year = 2022 | doi = 10.1073/pnas.2120006119 | doi-access = free | pmid = 35349345| pmc = 9168836 | bibcode = 2022PNAS..11920006L }}</ref><ref name="pmid35653469">{{cite journal |vauthors=Shaltiel IA, Datta S, Lecomte L, Hassler M, Kschonsak M, Bravo S, Stober C, Ormanns J, Eustermann S, Haering CH | title = A hold-and-feed mechanism drives directional DNA loop extrusion by condensin | journal = Science | volume = 376 | issue = 6597 | pages = 1087–1094 | year = 2022 | doi = 10.1126/science.abm4012 | pmid = 35653469| bibcode = 2022Sci...376.1087S }}</ref> A comparative analysis of human condensin I and condensin II has also been reported.<ref name="pmid32445620">{{cite journal |vauthors=Kong M, Cutts EE, Pan D, Beuron F, Kaliyappan T, Xue C, Morris EP, Musacchio A, Vannini A, Greene EC | title = Human Condensin I and II Drive Extensive ATP-Dependent Compaction of Nucleosome-Bound DNA | journal = Mol Cell | volume = 79 | issue = 1 | pages = 99–114.e9 | year = 2020 | pmid = 32445620 | doi = 10.1016/j.molcel.2020.04.026| pmc = 7335352 | hdl = 21.11116/0000-0006-73C9-6 | hdl-access = free }}</ref>

==Molecular activities== ===DNA compaction=== Among the various molecular activities attributed to condensins, perhaps the most intuitive is its ability to compact DNA by folding it, thereby reducing its effective length. Indeed, an early single-molecule experiment using magnetic tweezers have shown that condensin I purified from ''Xenopus'' egg metaphase extracts actively shortens the length of DNA in an ATP hydrolysis-dependent manner, and this process can be observed in real time.<ref name="pmid15186743">{{cite journal |vauthors=Strick TR, Kawaguchi T, Hirano T | title = Real-time detection of single-molecule DNA compaction by condensin I | journal = Curr Biol | volume = 14 | issue = 10 | pages = 874–880| year = 2004 | doi = 10.1016/j.cub.2004.04.038 | pmid = 15186743| bibcode = 2004CBio...14..874S }} </ref> More recently, a comparable yet less dynamic compaction process mediated by budding yeast condensin was observed in the same experimental setup<ref name="pmid29118001">{{cite journal |vauthors=Eeftens JM, Bisht S, Kerssemakers J, Kschonsak M, Haering CH, Dekker C | title = Real-time detection of condensin-driven DNA compaction reveals a multistep binding mechanism| journal = EMBO J | volume = 36 | issue = 23 | pages = 3448–3457 | year = 2017 | doi = 10.15252/embj.201797596| pmid = 29118001| pmc = 5709735}} </ref> Furthermore, optical tweezers–based assays combining single-molecule DNA manipulation with ''Xenopus'' egg extracts have revealed that, among the multiple DNA-compacting activities present in mitotic extracts, condensins make the dominant contribution.<ref name="pmid36917660">{{cite journal |vauthors=Sun M, Amiri H, Tong AB, Shintomi K, Hirano T, Bustamante C, Heald R | title = Monitoring the compaction of single DNA molecules in Xenopus egg extract in real time | journal = Proc Natl Acad Sci USA | volume = 120 | issue = 12 | article-number = e2221309120 | year = 2023 | doi = 10.1073/pnas.2221309120 | doi-access = free | pmid = 36917660| pmc = 10041109 | bibcode = 2023PNAS..12021309S }} </ref>

===DNA supercoiling=== Early studies using condensin I purified from ''Xenopus'' egg extracts demonstrated that the complex introduces positive supercoils into double-stranded DNA in an ATP hydrolysis–dependent manner, in the presence of type I topoisomerases.<ref name="pmid9288743">{{cite journal |vauthors=Kimura K, Hirano T | title =ATP-dependent positive supercoiling of DNA by 13S condensin: a biochemical implication for chromosome condensation | journal = Cell| volume = 90 | issue = 4 | pages = 625–634 | year = 1997 | doi =10.1016/s0092-8674(00)80524-3 | pmid = 9288743| doi-access = free }} </ref> Although this activity is often described as positive DNA supercoiling, it differs fundamentally from that of topoisomerases, since condensin I lacks DNA cleavage and re-ligation activity. Similar activities have also been observed with condensin complexes from nematodes and budding yeast.<ref name="pmid11914278">{{cite journal |vauthors=Hagstrom KA, Holmes VF, Cozzarelli NR, Meyer BJ | title = C. elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis | journal = Genes Dev| volume = 16 | issue = 6| pages = 729–742 | year = 2002 | doi = 10.1101/gad.968302 | pmid =11914278| pmc = 155363 }} </ref><ref name="pmid19481522">{{cite journal |vauthors=St-Pierre J, Douziech M, Bazile F, Pascariu M, Bonneil E, Sauvé V, Ratsima H, D'Amours D | title = Polo kinase regulates mitotic chromosome condensation by hyperactivation of condensin DNA supercoiling activity | journal = Mol Cell| volume = 120 | issue = Pt 7 | pages = 1245–1255 | year = 2009 | doi = 10.1016/j.molcel.2009.04.013 | pmid =19481522}} </ref> Furthermore, a modified assay combined with a type II topoisomerase has shown that ''Xenopus'' condensin I can generate "two oriented" supercoils in an ATP hydrolysis-dependent manner.<ref name="pmid10428035">{{cite journal |vauthors=Kimura K, Rybenkov VV, Crisona NJ, Hirano T, Cozzarelli NR | title =13S condensin actively reconfigures DNA by introducing global positive writhe: implications for chromosome condensation | journal = Cell| volume = 98 | issue = 2 | pages = 239–248 | year = 1999 | doi =10.1016/s0092-8674(00)81018-1 | pmid = 10428035| doi-access = free }} </ref> These activities are stimulated by Cdk1-mediated phosphorylation ''in vitro'', suggesting that they may constitute an essential mechanism underlying mitotic chromosome condensation.<ref name="pmid10428035">{{cite journal |vauthors=Kimura K, Rybenkov VV, Crisona NJ, Hirano T, Cozzarelli NR | title =13S condensin actively reconfigures DNA by introducing global positive writhe: implications for chromosome condensation | journal = Cell| volume = 98 | issue = 2 | pages = 239–248 | year = 1999 | doi =10.1016/s0092-8674(00)81018-1 | pmid = 10428035| doi-access = free }} </ref><ref name="pmid9774278">{{cite journal |vauthors=Kimura K, Hirano M, Kobayashi R, Hirano T | title =Phosphorylation and activation of 13S condensin by Cdc2 in vitro | journal = Science| volume = 282 | issue = 5388 | pages = 487–490 | year = 1998 | doi =10.1126/science.282.5388.487 | pmid = 9774278| bibcode =1998Sci...282..487K }} </ref> Through this supercoiling activity, condensin may not only facilitate chromatin compaction but also promote the resolution and separation of sister chromatids by aiding the action of topoisomerase II.<ref name="pmid21393545">{{cite journal |vauthors=Baxter J, Sen N, Martínez VL, De Carandini ME, Schvartzman JB, Diffley JF, Aragón L | title = Positive supercoiling of mitotic DNA drives decatenation by topoisomerase II in eukaryotes | journal = Science | volume = 331 | issue = 6022 | pages = 1328–1332 | year =2011 | doi = 10.1126/science.1201538 | pmid = 21393545| bibcode = 2011Sci...331.1328B }} </ref>

===DNA loop extrusion=== {{Main|Loop extrusion}} Among the various biochemical activities of condensins, loop extrusion has recently attracted the most attention. The concept of loop extrusion, where condensins actively "extrude" DNA to form loops, was first proposed theoretically and later supported by computer simulations.<ref name="pmid 27192037">{{cite journal |vauthors=Goloborodko A, Imakaev MV, Marko JF, Mirny L | title = Compaction and segregation of sister chromatids via active loop extrusion | journal = eLife | volume = 5 | article-number = e14864 | year = 2016 | doi = 10.7554/eLife.14864 | doi-access = free | pmid = 27192037| pmc = 4914367 }}</ref> Experimentally, budding yeast condensin was shown to translocate along double-stranded DNA in an ATP hydrolysis–dependent manner.<ref name="pmid28882993">{{cite journal |vauthors=Terakawa T, Bisht S, Eeftens JM, Dekker C, Haering CH, Greene EC | title = The condensin complex is a mechanochemical motor that translocates along DNA | journal = Science| volume = 358 | issue = 6363 | pages = 672–676 | year = 2017 | doi = 10.1126/science.aan6516 | pmid =28882993| pmc = 5862036 | bibcode = 2017Sci...358..672T }}</ref> This was soon followed by direct visualization of loop extrusion, in which condensin extrudes and enlarges DNA loops over time.<ref name="pmid28882993">{{cite journal |vauthors=Terakawa T, Bisht S, Eeftens JM, Dekker C, Haering CH, Greene EC | title = The condensin complex is a mechanochemical motor that translocates along DNA | journal = Science| volume = 358 | issue = 6363 | pages = 672–676 | year = 2017 | doi = 10.1126/science.aan6516 | pmid =28882993| pmc = 5862036 | bibcode = 2017Sci...358..672T }}</ref> Furthermore, condensin has been shown to bypass other condensin complexes upon collision on the same DNA molecule,<ref name="pmid32132705">{{cite journal |vauthors=Kim E, Kerssemakers J, Shaltiel IA, Haering CH, Dekker C | title = DNA-loop extruding condensin complexes can traverse one another | journal = Nature | volume = 579 | issue = 7799 | pages = 438–442 | year = 2020 | doi = 10.1038/s41586-020-2067-5 | pmid =32132705| bibcode = 2020Natur.579..438K }}</ref> and even traverse large obstacles significantly exceeding its own size.<ref name="pmid36261017">{{cite journal |vauthors=Pradhan B, Barth R, Kim E, Davidson IF, Bauer B, van Laar T, Yang W, Ryu JK, van der Torre J, Peters JM, Dekker C | title = SMC complexes can traverse physical roadblocks bigger than their ring size | journal = Cell Rep | volume = 41 | issue = 3 | article-number = 111491 | year = 2022 | doi = 10.1016/j.celrep.2022.111491 | pmid =36261017}}</ref>

The molecular mechanism underlying loop extrusion by condensins is an active area of investigation, with insights emerging from structural studies as well.<ref name="pmid35477004">{{cite journal |vauthors=Oldenkamp R, Rowland BD| title =A walk through the SMC cycle: From catching DNAs to shaping the genome| journal = Mol Cell | volume = 82 | issue = 9 | pages = 1616–1630 | year = 2022 | doi =10.1016/j.molcel.2022.04.006| pmid =35477004}} </ref><ref name="pmid37943927">{{cite journal |vauthors=Dekker C, Haering CH, Peters, JM, Rowland, BD | title = How do molecular motors fold the genome? | journal = Science | volume = 382| issue = 6671 | pages = 646–648 | year = 2023 | doi = 10.1126/science.adi8308 | pmid =37943927| bibcode = 2023Sci...382..646D | url = http://resolver.tudelft.nl/uuid:7fc47989-1d98-40b1-ba87-3bd189025859 }}</ref> Current models suggest that multiple condensin subunits interact with DNA in a coordinated manner, tightly coupled to the ATPase cycle of the SMC core subunits.<ref name="pmid28988770">{{cite journal | vauthors = Kschonsak M, Merkel F, Bisht S, Metz J, Rybin V, Hassler M, Haering CH| title =Structural basis for a safety-belt mechanism that anchors condensin to chromosomes | journal = Cell | volume = 171 | issue = 3 | pages = 588–600.e24 | year = 2017 | doi =10.1016/j.cell.2017.09.008 | pmid =28988770| pmc =5651216 }}</ref><ref name="pmid31226277">{{cite journal |vauthors=Hassler M, Shaltiel IA, Kschonsak M, Simon B, Merkel F, Thärichen L, Bailey HJ, Macošek J, Bravo S, Metz J, Hennig J, Haering CH| title =Structural basis of an asymmetric condensin ATPase cycle | journal = Mol Cell | volume = 74 | issue = 6 | pages = 1175–1188.e24 | year = 2019 | doi =10.1016/j.molcel.2019.03.037 | pmid =31226277| pmc =6591010 }}</ref><ref name="pmid35653469">{{cite journal |vauthors=Shaltiel IA, Datta S, Lecomte L, Hassler M, Kschonsak M, Bravo S, Stober C, Ormanns J, Eustermann S, Haering CH | title = A hold-and-feed mechanism drives directional DNA loop extrusion by condensin | journal = Science | volume = 376 | issue = 6597 | pages = 1087–1094 | year = 2022 | doi = 10.1126/science.abm4012 | pmid = 35653469| bibcode = 2022Sci...376.1087S }}</ref> These interactions are thought to be mechanistically intricate and highly dynamic. Some evidence also points to a potential link between condensin-mediated loop extrusion and supercoiling,<ref name="pmid35835864">{{cite journal |vauthors=Kim E, Gonzalez AM, Pradhan B, van der Torre J, Dekker C | title = Condensin-driven loop extrusion on supercoiled DNA | journal = Nat Struct Mol Biol | volume = 29 | issue = 7 | pages = 719–727 | year = 2022 | doi = 10.1038/s41594-022-00802-x | pmid =35835864}}</ref><ref name="pmid36533296">{{cite journal |vauthors=Martínez-García B, Dyson S, Segura J, Ayats A, Cutts EE, Gutierrez-Escribano P, Aragón L, Roca J | title = Condensin pinches a short negatively supercoiled DNA loop during each round of ATP usage | journal = EMBO J | article-number = e111913 | year = 2022 | volume = 42 | issue = 3 | doi = 10.15252/embj.2022111913 | pmid =36533296| pmc = 9890231 }}</ref><ref name="pmid39671477">{{cite journal |vauthors=Janissen R, Barth R, Davidson IF, Peters JM, Dekker C |title=All eukaryotic SMC proteins induce a twist of −0.6 at each DNA loop extrusion step |journal=Sci Adv |volume=10 |issue=50 |article-number=eadt1832 |year=2024 |pmid=39671477 |pmc=11641105 |doi=10.1126/sciadv.adt1832|bibcode=2024SciA...10.1832J }}</ref> although the exact mechanism of this link remains unclear. Moreover, whether and how mitosis-specific phosphorylation of condensin subunits modulates loop extrusion activity has yet to be fully elucidated.

===DNA loop capture=== Although accumulating evidence supports the loop extrusion model, direct evidence for its occurrence ''in vivo'' remains lacking. As an alternative, a mechanism termed "loop capture" (or "diffusion capture") has been proposed.<ref name="pmid33434270">{{cite journal |vauthors=Gerguri T, Fu X, Kakui Y, Khatri BS, Barrington C, Bates PA, Uhlmann F | title =Comparison of loop extrusion and diffusion capture as mitotic chromosome formation pathways in fission yeast | journal = Nucl Acids Res | volume = 49 | issue = 3 | pages = 1294–1312 | year = 2021 | doi =10.1093/nar/gkaa1270 | pmid = 33434270| pmc =7897502 }} </ref><ref name="pmid37820734">{{cite journal |vauthors=Tang M, Pobegalov G, Tanizawa H, Chen ZA, Rappsilber J, Molodtsov M, Noma KI, Uhlmann F | title = Establishment of dsDNA-dsDNA interactions by the condensin complex| journal = Mol Cell | volume = 83 | issue = 21 | pages = 3787–3800 | year = 2023 | doi = 10.1016/j.molcel.2023.09.019| pmid = 37820734| pmc = 10842940}} </ref><ref name="pmid40118039">{{cite journal |vauthors=Uhlmann F | title =A unified model for cohesin function in sister chromatid cohesion and chromatin loop formation | journal = Mol Cell | volume = 85 | issue = 6 | pages = 1058–1071 | year = 2025 | doi =10.1016/j.molcel.2025.02.005 | pmid = 40118039| doi-access = free }} </ref> In this model, a condensin complex initially binds one segment of DNA and then captures a second DNA segment that comes into close proximity along the same DNA molecule, thereby forming a DNA loop. Unlike loop extrusion, loop capture does not require active translocation along DNA; instead, loops form through thermodynamic fluctuations. Loop capture and loop extrusion may not be necessarily mutually exclusive and may function in parallel within cells to promote DNA loop formation and expansion.

===Chromosome assembly and reconstitution=== The supercoiling and loop extrusion activities of condensin have been primarily demonstrated using experiments with naked DNA as the substrate. To investigate condensin function under more physiological conditions, a powerful ''in vitro'' assay using ''Xenopus'' egg extracts has been in use.<ref name="pmid9160743">{{cite journal | vauthors = Hirano T, Kobayashi R, Hirano M | title = Condensins, chromosome condensation complex containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein | journal = Cell | volume = 89 | issue = 4 | pages = 511–21 | year = 1997 | pmid = 9160743 | doi=10.1016/S0092-8674(00)80233-0| s2cid = 15061740 | doi-access = free}}</ref> In this system, metaphase extracts prepared from unfertilized ''Xenopus'' eggs are used to recapitulate mitotic chromosome assembly in a test tube. By immunodepleting endogenous condensin from extracts and supplementing them with wild-type or mutant recombinant condensin complexes, researchers can evaluate the contribution of specific subunits or mutations to chromosome assembly activity. This system has demonstrated that both ATP binding and hydrolysis by the SMC subunits of condensin I are essential for chromosome assembly. It also revealed that the antagonistic actions of the two HEAT-repeat subunits, as well as condensin–condensin interactions, are critical for the dynamic organization of chromosome axes.<ref name="pmid25850674">{{cite journal |vauthors=Kinoshita K, Kobayashi TJ, Hirano T| title = Balancing acts of two HEAT subunits of condensin I support dynamic assembly of chromosome axes | journal = Dev Cell | volume = 33 | issue = 1 | pages = 94–106 | year = 2015 | doi = 10.1016/j.devcel.2015.01.034 | pmid = 25850674}}</ref><ref name="pmid35045152">{{cite journal |vauthors=Kinoshita K, Tsubota Y, Tane S, Aizawa Y, Sakata R, Takeuchi K, Shintomi K, Nishiyama T, Hirano T | title = A loop extrusion-independent mechanism contributes to condensin I-mediated chromosome shaping | journal = J Cell Biol | volume = 221 | issue = 3 | article-number = e202109016 | year = 2022 | doi = 10.1083/jcb.202109016 | pmid = 35045152| pmc = 8932526 }}</ref><ref name="pmid41208622">{{cite journal |vauthors=Kinoshita K, Aizawa Y, Hirano T | title = Condensin-condensin interactions facilitate mitotic chromosome assembly in Xenopus egg extracts | journal = Genes Cells | volume = 30 | pages = e70065 | year = 2025 | pmid = 41208622 }}</ref> Moreover, linker histones have been shown to compete with condensins, thereby modulating chromosome morphology in this system.<ref>{{cite journal |vauthors=Choppakatla P, Dekker B, Cutts EE, Vannini A, Dekker J, Funabiki H |year=2021|title=Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization |journal=eLife| volume=10 | article-number = e68918 |doi=10.7554/eLife.68918 |doi-access=free | pmid =34406118|pmc=8416026 }}</ref> Remarkably, even under nucleosome-depleted conditions, the extract is capable of assembling chromosome-like structures in a manner dependent on condensins and topoisomerase II.<ref>{{cite journal |vauthors=Shintomi K, Inoue F, Watanabe H, Ohsumi K, Ohsugi M, Hirano T|year=2017|title=Mitotic chromosome assembly despite nucleosome depletion in ''Xenopus'' egg extracts|journal=Science| volume=356 | issue = 6344 | pages = 1284–1287 |doi=10.1126/science.aam9702 | pmid =28522692|bibcode=2017Sci...356.1284S }}</ref> This observation indicates that condensins possess biologically relevant activity on nucleosome-free DNA, further highlighting their central role in chromosome architecture beyond its interaction with chromatinized templates.

More recently, an ''in vitro'' chromosome reconstitution system using purified proteins has been developed, confirming the essential role of condensin I in chromosome assembly.<ref name="pmid26075356">{{cite journal |vauthors=Shintomi K, Takahashi TS, Hirano T | title = Reconstitution of mitotic chromatids with a minimum set of purified factors | journal = Nat Cell Biol | volume = 17 | issue = 8 | pages = 1014–1023 | year = 2015 | doi = 10.1038/ncb3187 | pmid = 26075356}} </ref><ref name="pmid34006877">{{cite journal |vauthors=Shintomi K, Hirano T | title = Guiding functions of the C-terminal domain of topoisomerase IIα advance mitotic chromosome assembly | journal = Nat Commun | volume = 12 | issue = 1 | page = 2917 | year = 2021 | doi = 10.1038/s41467-021-23205-w | pmid = 34006877| pmc = 8131626 | bibcode = 2021NatCo..12.2917S }} </ref> In this system, chromosomes can be reconstituted from a simple substrate (sperm nuclei) by supplementing with only six purified components: core histones, three types of histone chaperones, topoisomerase II, and condensin I. For condensin I to exert its chromosome assembly activity in this reconstitution system, it must be phosphorylated by the mitotic kinase cyclin B-Cdk1. Among the essential histone chaperones identified, FACT (Facilitates Chromatin Transcription) transiently destabilizes and reassembles nucleosomes, thereby facilitating the folding of nucleosomal fibers by condensin I and topoisomerase II.

===Condensin I vs condensin II=== How similar or how different are the molecular activities of condensin I and condensin II? Both complexes share the same two SMC subunits (SMC2 and SMC4), but each has a distinct set of three non-SMC subunits (see Fig. 2). Subtle differences in the balance of these non-SMC subunits are thought to account for differences in loop formation speed<ref name="pmid 32445620">{{cite journal |vauthors=Kong M, Cutts EE, Pan D, Beuron F, Kaliyappan T, Xue C, Morris EP, Musacchio A, Vannini A, Greene EC | title = Human condensin I and II drive extensive ATP-dependent compaction of nucleosome-bound DNA | journal = Mol. Cell | volume = 79 | issue = 1 | pages = 99–114 | year = 2020 | doi = 10.1016/j.molcel.2020.04.026 | pmid = 32445620| pmc = 7335352 }} </ref> and chromosome assembly activity<ref name="pmid25850674">{{cite journal |vauthors=Kinoshita K, Kobayashi TJ, Hirano T| title = Balancing acts of two HEAT subunits of condensin I support dynamic assembly of chromosome axes | journal = Dev Cell | volume = 33 | issue = 1 | pages = 94–106 | year = 2015 | doi = 10.1016/j.devcel.2015.01.034 | pmid = 25850674}}</ref><ref name="pmid35045152">{{cite journal |vauthors=Kinoshita K, Tsubota Y, Tane S, Aizawa Y, Sakata R, Takeuchi K, Shintomi K, Nishiyama T, Hirano T | title = A loop extrusion-independent mechanism contributes to condensin I-mediated chromosome shaping | journal = J Cell Biol | volume = 221 | issue = 3 | article-number = e202109016 | year = 2022 | doi = 10.1083/jcb.202109016 | pmid = 35045152| pmc = 8932526 }}</ref><ref name="pmid 35983835">{{cite journal |vauthors=Yoshida MM, Kinoshita K, Aizawa Y, Tane S, Yamashita D, Shintomi K, Hirano T | title = Molecular dissection of condensin II-mediated chromosome assembly using in vitro assays | journal = eLife | volume = 11 | article-number = e78984 | year = 2022 | doi = 10.7554/eLife.78984 | doi-access = free | pmid = 35983835| pmc = 9433093 }} </ref><ref name="pmid38088875">{{cite journal |vauthors=Yoshida MM, Kinoshita K, Shintomi K, Aizawa Y, Hirano T | title = Regulation of condensin II by self-suppression and release mechanisms | journal = Mol Biol Cell | volume = 35 | issue = 2 | pages = ar21 | year = 2024 | doi = 10.1091/mbc.E23-10-0392 | pmid = 38088875| pmc = 10881152 }} </ref> between the two complexes. Interestingly, experimental studies have shown that by introducing specific mutations, it is possible to convert condensin I into a complex with condensin II-like activity. Likewise, condensin II can be engineered to exhibit condensin I-like properties.<ref name="pmid38088875">{{cite journal |vauthors=Yoshida MM, Kinoshita K, Shintomi K, Aizawa Y, Hirano T | title = Regulation of condensin II by self-suppression and release mechanisms | journal = Mol Biol Cell | volume = 35 | issue = 2 | pages = ar21 | year = 2024 | doi = 10.1091/mbc.E23-10-0392 | pmid = 38088875| pmc = 10881152 }} </ref>

===Mathematical modeling and computer simulations=== Several mathematical modeling and computer simulation studies of mitotic chromosome assembly, based on the molecular activities of condensins, have been reported. Representative ones include modeling based on loop extrusion,<ref name="pmid 27192037">{{cite journal |vauthors=Goloborodko A, Imakaev MV, Marko JF, Mirny L | title = Compaction and segregation of sister chromatids via active loop extrusion | journal = eLife | volume = 5 | article-number = e14864 | year = 2016 | doi = 10.7554/eLife.14864 | doi-access = free | pmid = 27192037| pmc = 4914367 }}</ref> loop capture,<ref name="pmid33434270">{{cite journal |vauthors=Gerguri T, Fu X, Kakui Y, Khatri BS, Barrington C, Bates PA, Uhlmann F | title =Comparison of loop extrusion and diffusion capture as mitotic chromosome formation pathways in fission yeast | journal = Nucl Acids Res | volume = 49 | issue = 3 | pages = 1294–1312 | year = 2021 | doi =10.1093/nar/gkaa1270 | pmid = 33434270| pmc =7897502 }} </ref> a combination of looping and condensin-condensin interactions,<ref name="pmid 29912867">{{cite journal |last1=Sakai |first1=Yuji |last2=Mochizuki |first2=Atsushi |last3=Kinoshita |first3=Kazuhisa |last4=Hirano |first4=Tatsuya |last5=Tachikawa |first5=Masashi |last6=Morozov |first6=Alexandre V. |title=Modeling the functions of condensin in chromosome shaping and segregation |journal=PLOS Computational Biology |date=18 June 2018 |volume=14 |issue=6 |article-number=e1006152 |doi=10.1371/journal.pcbi.1006152 |pmid=29912867 |pmc=6005465 |bibcode=2018PLSCB..14E6152S |doi-access=free }}</ref> and bridging-induced attraction.<ref name="pmid37976091">{{cite journal |vauthors=Forte G, Boteva L, Conforto F, Gilbert N, Cook PR, Marenduzzo D| title = Bridging condensins mediate compaction of mitotic chromosomes| journal = J Cell Biol | volume = 223 | issue = 1 | article-number = e202209113 | year = 2024 | doi = 10.1083/jcb.202209113| pmid = 37976091| pmc = 10655892}}</ref>

==Functions in chromosome assembly and segregation== ===Mitosis=== 600px|thumb|Figure 5. Chromosome dynamics during mitosis in eukaryotes 200px|thumb|Figure 6. Distribution of condensin I (green) and condensin II (red) in human metaphase chromosomes. Bar, 1 μm. In human tissue culture cells, the two condensin complexes are regulated differently during the mitotic cell cycle (Figure 5).<ref name="pmid15146063">{{cite journal | vauthors = Ono T, Fang Y, Spector DL, Hirano T | title =Spatial and temporal regulation of Condensins I and II in mitotic chromosome assembly in human cells | journal = Mol. Biol. Cell| volume = 15 | issue = 7 | pages = 3296–308 | year = 2004 | pmid = 15146063 | doi=10.1091/mbc.E04-03-0242 | pmc=452584}}</ref><ref name="pmid15572404">{{cite journal | vauthors = Hirota T, Gerlich D, Koch B, Ellenberg J, Peters JM | title = Distinct functions of condensin I and II in mitotic chromosome assembly | journal = J. Cell Sci.| volume = 117 | issue = Pt 26 | pages = 6435–45 | year = 2004 | pmid = 15572404 | doi=10.1242/jcs.01604| doi-access = free }}</ref> Condensin II is present within the cell nucleus during interphase and participates in an early stage of chromosome condensation within the prophase nucleus. On the other hand, condensin I is present in the cytoplasm during interphase, and gains access to chromosomes only after the nuclear envelope breaks down (NEBD) at the end of prophase. During prometaphase and metaphase, condensin I and condensin II cooperate to assemble rod-shaped chromosomes, in which two sister chromatids are fully resolved.

Such differential dynamics of the two complexes is observed in ''Xenopus'' egg extracts,<ref name="pmid21715560">{{cite journal | vauthors = Shintomi K, Hirano T | title =The relative ratio of condensin I to II determines chromosome shapes | journal = Genes Dev. | volume = 25 | issue = 14 | pages = 1464–9 | year = 2011 | doi =10.1101/gad.2060311 | pmid = 21715560| pmc =3143936 }}</ref> mouse oocytes,<ref name="pmid21795393">{{cite journal | vauthors = Lee J, Ogushi S, Saitou M, Hirano T| title = Condensins I and II are essential for construction of bivalent chromosomes in mouse oocytes| journal = Mol. Biol. Cell| volume = 22 | issue = 18 | pages = 3465–77 | year = 2011| doi = 10.1091/mbc.E11-05-0423| pmid = 21795393| pmc = 3172270}}</ref> and neural stem cells,<ref name="pmid25474630">{{cite journal |vauthors=Nishide K, Hirano T| title = Overlapping and non-overlapping functions of condensins I and II in neural stem cell divisions| journal = PLOS Genet| volume = 10 | issue = 12 | article-number = e1004847| year = 2014 | doi = 10.1371/journal.pgen.1004847| doi-access = free| pmid = 25474630 | pmc = 4256295}}</ref> indicating that it is part of a fundamental regulatory mechanism conserved among different organisms and cell types. Indeed, recent studies have shown that forced localization of condensin I to the interphase nucleus can lead to abnormal chromosome segregation during subsequent mitosis.<ref name="pmid40107266">{{cite journal |vauthors=Eykelenboom JK, Gierliński M, Yue Z, Tanaka TU | title = Nuclear exclusion of condensin I in prophase coordinates mitotic chromosome reorganization to ensure complete sister chromatid resolution | journal = Curr Biol | volume = 35 | issue = 7 | pages = 1562–1575e | year = 2025 | doi = 10.1016/j.cub.2025.02.047 | pmid = 40107266| bibcode = 2025CBio...35.1562E | doi-access = free }}</ref> It is most likely that this mechanism ensures the ordered action of the two complexes, namely, condensin II first and condensin I later.<ref name="pmid22855829">{{cite journal | vauthors = Hirano T | title = Condensins: universal organizers of chromosomes with diverse functions | journal = Genes Dev | volume = 26 | issue = 4 | pages =1659–78 | year = 2012| doi = 10.1101/gad.194746.112 | pmid = 22855829| pmc = 3418584 }}</ref>

On metaphase chromosomes, condensins I and II are both enriched in the central axis in a non-overlapping fashion (Figure 6). Depletion experiments ''in vivo''<ref name="pmid14532007"/><ref name="pmid25474630"/><ref name="pmid22344259">{{cite journal | vauthors = Green LC, Kalitsis P, Chang TM, Cipetic M, Kim JH, Marshall O, Turnbull L, Whitchurch CB, Vagnarelli P, Samejima K, Earnshaw WC, Choo KH, Hudson DF | title = Contrasting roles of condensin I and condensin II in mitotic chromosome formation | journal = J. Cell Sci. | volume = 125 | issue = Pt6 | pages = 1591–1604 | year = 2012 | doi = 10.1242/jcs.097790 | pmid = 22344259| pmc = 3336382 }}</ref> and immunodepletion experiments in ''Xenopus'' egg extracts<ref name="pmid21715560"/> demonstrate that the two complexes have distinct functions in assembling metaphase chromosomes. Cells deficient in condensin functions are not arrested at a specific stage of cell cycle, displaying chromosome segregation defects (i.e., anaphase bridges) and progressing through abnormal cytokinesis.<ref name="pmid12919682">{{cite journal | vauthors = Hudson DF, Vagnarelli P, Gassmann R, Earnshaw WC | title = Condensin is required for nonhistone protein assembly and structural integrity of vertebrate mitotic chromosomes | journal = Dev. Cell| volume = 5 | issue = 2 | pages = 323–336 | year = 2003 | doi = 10.1016/s1534-5807(03)00199-0 | pmid = 12919682| doi-access =free }}</ref>

The requirement for condensin I and II in mitosis varies among species. *In mice (''Mus musculus''), both condensin I and condensin II are essential for embryonic development, as shown by gene knockout experiments.<ref name="pmid25474630"/> The two complexes exhibit partially overlapping but also distinct functions during mitosis. *The primitive red alga ''C. merolae''<ref name="pmid23783031"/> and the land plant ''A. thaliana''<ref name="pmid21917552">{{cite journal | vauthors = Sakamoto T, Inui YT, Uraguchi S, Yoshizumi T, Matsunaga S, Mastui M, Umeda M, Fukui K, Fujiwara T| title = Condensin II alleviates DNA damage and is essential for tolerance of boron overload stress in Arabidopsis| journal = Plant Cell| volume = 23 | issue = 9 | pages = 3533–46 | year = 2011 | doi = 10.1105/tpc.111.086314| pmid = 21917552| pmc = 3203421| bibcode = 2011PlanC..23.3533S}}</ref> possess both condensin I and II, yet condensin II is dispensable for mitotic chromosome segregation in these species. *In the early embryos of the nematode ''C. elegans'', condensin II plays a predominant role, effectively reversing the typical functional relationship between the two complexes.<ref name="pmid19119011"/> This may be related to the organism's holocentric chromosomes, in which kinetochores are distributed along the entire chromosome length. *In the fruit fly ''D. melanogaster'', one of the condensin II–specific subunits (CAP-G2) is missing. The remaining condensin II subunits, CAP-D3 and CAP-H2, are not essential for mitosis but play significant roles in meiosis.<ref name="pmid19039137">{{cite journal | vauthors = Hartl TA, Smith HF, Bosco G | title =Chromosome alignment and transvection are antagonized by condensin II. | journal = Science | volume = 322 | issue = 5906 | pages = 1384–7 | year = 2008 | pmid = 19039137 | doi=10.1126/science.1164216| bibcode =2008Sci...322.1384H | s2cid =5154197 }}</ref> *Some fungi, including ''S. cerevisiae'' and ''S. pombe'', lack condensin II altogether.<ref name="pmid10485849"/><ref name="pmid10811823"/> In these organisms, condensin I functions in both mitosis and meiosis.

These species-specific differences offer valuable insights into the evolution of chromosome architecture and genome size (see also the section "Evolutionary implications"). The following table summarizes the requirement for condensin I and II during mitosis in representative eukaryotic model organisms. {| class="wikitable" |- ! species !! ''M. musculus'' !! ''D. melanogaster'' !! ''C. elegans'' !! ''S. cerevisiae'' !! ''S. pombe'' !! ''A. thaliana'' !! ''C. merolae'' |- | genome size || ~2,500 Mb || 140 Mb || 100 Mb || 12 Mb || 14 Mb || 125 Mb || 16 Mb |- | condensin I || essential || essential || ? || essential || essential || essential || essential |- | condensin II|| essential || non-essential || essential || - || - || non-essential || non-essential |- |}

It has recently become possible that cell cycle-dependent structural changes of chromosomes are monitored by a genomics-based method known as Hi-C (High-throughput chromosome conformation capture).<ref name="pmid 24200812">{{cite journal | vauthors = Naumova N, Imakaev M, Fudenberg G, Zhan Y, Lajoie BR, Mirny LA, Dekker J| title = Organization of the mitotic chromosome| journal = Science | volume = 342 | issue = 6161 | pages = 948–953 | year = 2013| doi = 10.1126/science.1236083| pmid = 24200812| pmc = 4040465| bibcode = 2013Sci...342..948N}}</ref> The impact of condensin deficiency on chromosome conformation has been addressed in budding yeast,<ref name="pmid 28825700">{{cite journal | vauthors = Schalbetter SA, Goloborodko A, Fudenberg G, Belton JM, Miles C, Yu M, Dekker J, Mirny L, Baxter J| title = SMC complexes differentially compact mitotic chromosomes according to genomic context| journal = Nat Cell Biol | volume = 19 | issue = 9 | pages = 1071–80 | year = 2017| doi = 10.1038/ncb3594| pmid = 28825700| pmc = 5640152}}</ref><ref name="pmid 28729434">{{cite journal | vauthors = Lazar-Stefanita L, Scolari VF, Mercy G, Muller H, Guérin TM, Thierry A, Mozziconacci J, Koszul R| title = Cohesins and condensins orchestrate the 4D dynamics of yeast chromosomes during the cell cycle| journal = EMBO J | volume = 36 | issue = 18 | pages = 2684–97 | year = 2017| doi = 10.15252/embj.201797342| pmid = 28729434| pmc = 5599795}}</ref> fission yeast,<ref name="pmid 28825727">{{cite journal | vauthors = Kakui Y, Rabinowitz A, Barry DJ, Uhlmann F| title = Condensin-mediated remodeling of the mitotic chromatin landscape in fission yeast| journal = Nat Genet | volume = 49 | issue = 10 | pages = 1553–7 | year = 2017| doi = 10.1038/ng.3938| pmid = 28825727| pmc = 5621628}}</ref><ref name="pmid 28991264">{{cite journal | vauthors = Tanizawa H, Kim KD, Iwasaki O, Noma KI| title = Architectural alterations of the fission yeast genome during the cell cycle| journal = Nat Struct Mol Biol| volume = 24 | issue = 11 | pages = 965–976 | year = 2017| doi = 10.1038/nsmb.3482| pmid = 28991264| pmc = 5724045}}</ref> and the chicken DT40 cells.<ref name="pmid 29348367">{{cite journal |last1=Gibcus |first1=Johan H. |last2=Samejima |first2=Kumiko |last3=Goloborodko |first3=Anton |last4=Samejima |first4=Itaru |last5=Naumova |first5=Natalia |last6=Nuebler |first6=Johannes |last7=Kanemaki |first7=Masato T. |last8=Xie |first8=Linfeng |last9=Paulson |first9=James R. |last10=Earnshaw |first10=William C. |last11=Mirny |first11=Leonid A. |last12=Dekker |first12=Job |title=A pathway for mitotic chromosome formation |journal=Science |date=9 February 2018 |volume=359 |issue=6376 |article-number=eaao6135 |doi=10.1126/science.aao6135 |pmid=29348367 |pmc=5924687 }}</ref> The outcome of these studies strongly supports the notion that condensins play crucial roles in mitotic chromosome assembly and that condensin I and II have distinct functions in this process. Moreover, quantitative imaging analyses allow researchers to count the number of condensin complexes present on human metaphase chromosomes.<ref name="pmid29632028">{{cite journal |last1=Walther |first1=Nike |last2=Hossain |first2=M. Julius |last3=Politi |first3=Antonio Z. |last4=Koch |first4=Birgit |last5=Kueblbeck |first5=Moritz |last6=Ødegård-Fougner |first6=Øyvind |last7=Lampe |first7=Marko |last8=Ellenberg |first8=Jan |title=A quantitative map of human Condensins provides new insights into mitotic chromosome architecture |journal=Journal of Cell Biology |date=2 July 2018 |volume=217 |issue=7 |pages=2309–28 |doi=10.1083/jcb.201801048 |pmid=29632028 |pmc=6028534 }}</ref>

===Meiosis=== Condensins also play important roles in chromosome assembly and segregation in meiosis. Genetic studies have been reported in ''S. cerevisiae,''<ref name="pmid14662740">{{cite journal | vauthors = Yu HG, Koshland DE| title =Meiotic condensin is required for proper chromosome compaction, SC assembly, and resolution of recombination-dependent chromosome linkages| journal = J. Cell Biol.| volume = 163 | issue = 5 | pages = 937–947 | year = 2003| doi =10.1083/jcb.200308027| pmid = 14662740| pmc =2173617}}</ref> ''D. melanogaster,''<ref name="pmid18927632">{{cite journal | vauthors = Hartl TA, Sweeney SJ, Knepler PJ, Bosco G| title =Condensin II resolves chromosomal associations to enable anaphase I segregation in Drosophila male meiosis| journal = PLOS Genet.| volume = 4 | issue = 10 | article-number = e1000228 | year = 2008| doi =10.1371/journal.pgen.1000228| pmid = 18927632| pmc =2562520| doi-access =free}}</ref><ref name="pmid19104074">{{cite journal | vauthors = Resnick TD, Dej KJ, Xiang Y, Hawley RS, Ahn C, Orr-Weaver TL| title =Mutations in the chromosomal passenger complex and the condensin complex differentially affect synaptonemal complex disassembly and metaphase I configuration in Drosophila female meiosis| journal = Genetics| volume = 181 | issue = 3 | pages = 875–887 | year = 2009| doi =10.1534/genetics.108.097741| pmid = 19104074| pmc =2651061}}</ref> and ''C. elegans''.<ref name="pmid15557118">{{cite journal | vauthors = Chan RC, Severson AF, Meyer BJ| title = Condensin restructures chromosomes in preparation for meiotic divisions| journal = J. Cell Biol.| volume = 167 | issue = 4 | pages = 613–625 | year = 2004| doi = 10.1083/jcb.200408061| pmid = 15557118| pmc = 2172564}}</ref> In mice, requirements for condensin subunits in meiosis have been addressed by antibody-mediated blocking experiments<ref name="pmid21795393"/> and conditional gene knockout analyses.<ref name="pmid25961503">{{cite journal | vauthors = Houlard M, Godwin J, Metson J, Lee J, Hirano T, Nasmyth K| title = Condensin confers the longitudinal rigidity of chromosomes| journal = Nat Cell Biol | volume = 17 | year = 2015 | issue = 6| pages = 771–81| doi = 10.1038/ncb3167| pmid = 25961503| pmc = 5207317}}</ref> In mammalian meiosis I, the functional contribution of condensin II appears bigger than that of condensin I. As has been shown in mitosis,<ref name="pmid25474630"/> however, the two condensin complexes have both overlapping and non-overlapping functions, too, in meiosis. Unlike cohesin, no meiosis-specific subunits of condensins have been identified so far.

==Chromosomal functions outside of mitosis or meiosis== Recent studies have shown that condensins participate in a wide variety of chromosome functions outside of mitosis or meiosis. *In ''S. cerevisiae'', condensin I (the sole condensin in this organism) is involved in copy number regulation of the rDNA repeat<ref name="pmid16507999">{{cite journal | vauthors = Johzuka K, Terasawa M, Ogawa H, Ogawa T, Horiuchi T | title = Condensin loaded onto the replication fork barrier site in the rRNA gene repeats during S phase in a FOB1-dependent fashion to prevent contraction of a long repetitive array in Saccharomyces cerevisiae. | journal = Mol Cell Biol | volume = 26 | issue = 6 | pages = 2226–36 | year = 2006 | pmid = 16507999 | doi=10.1128/MCB.26.6.2226-2236.2006 | pmc=1430289}}</ref> as well as in clustering of the tRNA genes.<ref name="pmid18708579">{{cite journal | vauthors = Haeusler RA, Pratt-Hyatt M, Good PD, Gipson TA, Engelke DR | title = Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes. | journal = Genes Dev. | volume = 22 | issue = 16 | pages = 2204–14 | year = 2008 | pmid = 18708579 | doi=10.1101/gad.1675908 | pmc=2518813}}</ref> *In ''S. pombe'', condensin I is involved in the regulation of replicative checkpoint<ref name="pmid12000964">{{cite journal | vauthors = Aono N, Sutani T, Tomonaga T, Mochida S, Yanagida M | title = Cnd2 has dual roles in mitotic condensation and interphase | journal = Nature | volume = 417 | issue = 6885 | pages = 197–202 | year = 2002 | doi = 10.1038/417197a | pmid = 12000964| bibcode = 2002Natur.417..197A | s2cid = 4332524 }}</ref> and clustering of genes transcribed by RNA polymerase III.<ref name="pmid19910488">{{cite journal | vauthors = Iwasaki O, Tanaka A, Tanizawa H, Grewal SI, Noma K | title =Centromeric localization of dispersed Pol III genes in fission yeast | journal = Mol. Biol. Cell | volume = 21 | issue = 2 | pages = 254–265 | year = 2010 | doi =10.1091/mbc.e09-09-0790 | pmid = 19910488| pmc =2808234 }}</ref> Some of the newly isolated mutants exhibiting temperature-sensitive and/or DNA damage-sensitive phenotypes were found to carry mutations in the HEAT subunits of condensin, indicating that these subunits play a role in proper DNA repair.<ref name = Xu2015>{{cite journal |vauthors=Xu X, Nakazawa N, Yanagida M |title=Condensin HEAT subunits required for DNA repair, kinetochore/centromere function and ploidy maintenance in fission yeast |journal=PLOS ONE |volume=10 |issue=3 |article-number=e0119347 |date=2015 |pmid=25764183 |pmc=4357468 |doi=10.1371/journal.pone.0119347 |doi-access=free|bibcode=2015PLoSO..1019347X }}</ref> *While early studies suggested that condensins might directly regulate gene expression, more recent findings have challenged this hypothesis at least in yeast.<ref name="pmid 29970489">{{cite journal | vauthors = Paul MR, Markowitz TE, Hochwagen A, Ercan S| title = Condensin depletion causes genome decompaction without altering the level of global gene expression in Saccharomyces cerevisiae| journal = Genetics | volume = 210 | issue = 1 | pages =331–344 | year = 2018 | doi = 10.1534/genetics.118.301217| pmid = 29970489 | pmc = 6116964}}</ref><ref name="pmid 30230473">{{cite journal | vauthors = Hocquet C, Robellet X, Modolo L, Sun XM, Burny C, Cuylen-Haering S, Toselli E, Clauder-Münster S, Steinmetz L, Haering CH, Marguerat S, Bernard P | title = Condensin controls cellular RNA levels through the accurate segregation of chromosomes insteadof directly regulating transcription| journal = eLife | volume = 7 | article-number = e38517 | year = 2018 | doi = 10.7554/eLife.38517| pmid = 30230473| pmc = 6173581| doi-access = free}}</ref> *In ''C. elegans'', a third condensin complex (condensin I^DC) related to condensin I regulates higher-order structure of X chromosomes as a major regulator of dosage compensation.<ref name="pmid26030525">{{cite journal | vauthors = Crane E, Bian Q, McCord RP, Lajoie BR, Wheeler BS, Ralston EJ, Uzawa S, Dekker J, Meyer BJ| title = Condensin-driven remodelling of X chromosome topology during dosage compensation | journal = Nature | volume = 523 | issue = 7559 | pages = 210–244 | year = 2015 | doi = 10.1038/nature14450 | pmid = 26030525| pmc = 4498965 | bibcode = 2015Natur.523..240C }}</ref> Curiously, in this species, condensin I not only fulfills a role analogous to that of vertebrate cohesin in organizing interphase chromosomes,<ref name="pmid39039278"/> but also coexists with a unique SMC-like protein called SMCL-1.<ref name="pmid28301465">{{cite journal |vauthors=Chao LF, Singh M, Thompson J, Yates JR 3rd, Hagstrom KA | title = An SMC-like protein binds and regulates Caenorhabditis elegans condensins | journal = PLOS Genet | volume = 13 | issue = 3 | article-number = e1006614 | year = 2017 | pmid = 28301465 | doi = 10.1371/journal.pgen.1006614| doi-access = free | pmc = 5373644 }}</ref> SMCL-1 is a small protein that lacks the hinge and coiled-coil domains typical of SMC proteins, and functions as a negative regulator of condensins. Notably, SMCL-1 is found only in ''Caenorhabditis'' species that also possess condensin I^DC, suggesting that it evolved to enable fine-tuned regulation of the two condensin I complexes. *In ''D. melanogaster'', condensin II subunits contribute to the dissolution of polytene chromosomes<ref name="pmid19039137"/> and the formation of chromosome territories<ref name="pmid22956908">{{cite journal | vauthors = Bauer CR, Hartl TA, Bosco G | title =Condensin II promotes the formation of chromosome territories by inducing axial compaction of polyploid interphase chromosomes. | journal = PLOS Genet | volume = 8 | issue = 8 | article-number = e1002873 | year = 2012 | pmid = 22956908 | doi=10.1371/journal.pgen.1002873 | pmc=3431300 | doi-access =free }}</ref> in ovarian nurse cells. Evidence is available that they negatively regulate transvection in diploid cells. It has also been reported that condensin I components are required to ensure correct gene expression in neurons following cell-cycle exit.<ref name="pmid32255428">{{cite journal |vauthors=Hassan A, Araguas Rodriguez P, Heidmann SK, Walmsley EL, Aughey GN, Southall TD | title =Condensin I subunit Cap-G is essential for proper gene expression during the maturation of post-mitotic neurons | journal = eLife | volume = 9 | article-number = e55159 | year = 2020 | doi =10.7554/eLife.55159 | pmid = 32255428| pmc =7170655 | doi-access = free }}</ref> *In ''A. thaliana'', condensin II is essential for tolerance of excess boron stress, possibly by alleviating DNA damage.<ref name="pmid21917552"/> *In mammalian cells, it is likely that condensin II is involved in the regulation of interphase chromosome architecture and function. For instance, in human cells, condensin II participates in the initiation of sister chromatid resolution during S phase, long time before mitotic prophase when sister chromatids become cytologically visible.<ref name="pmid23401001">{{cite journal | vauthors = Ono T, Yamashita D, Hirano T| title = Condensin II initiates sister chromatid resolution during S phase| journal = J. Cell Biol.| volume = 200 | issue = 4 | pages = 429–441| year = 2013 | doi = 10.1083/jcb.201208008| pmid =23401001| pmc = 3575537}}</ref> Moreover, a recent study has demonstrated that condensin II collaborates with cohesin to establish and maintain interphase chromosome territories.<ref name="pmid41511405">{{cite journal |vauthors=Ono T, Takagi M, Tanabe H, Fujita T, Saitoh N, Kimura A, Hirano T | title = Condensin II collaborates with cohesin to establish and maintain interphase chromosome territories | journal = J Cell Biol | volume = 225 | pages = e202511114 | year = 2026 | pmid = 41511405 }}</ref> *In mouse interphase nuclei, pericentromeric heterochromatin on different chromosomes associates with each other, forming a large structure known as chromocenters. Cells deficient in condensin II, but not in condensin I, display hyperclustering of chromocenters, indicating that condensin II has a specific role in suppressing chromocenter clustering.<ref name="pmid25474630"/>

==Regulation== ===Spatiotemporal regulation=== 600px|thumb|Figure 7. Spatiotemporal regulation of condensins Condensin activity is subject to spatiotemporal regulation during the cell cycle, although the specific regulatory patterns vary among species. * Most fungi possess only a single condensin complex. Many fungal species undergo "closed mitosis", in which the nuclear envelope remains intact throughout mitosis. In ''S. cerevisiae'', condensin remains in the nucleus throughout the cell cycle, and becomes active during mitosis to promote chromosome condensation (Figure 7). In contrast, in ''S. pombe'', condensin is localized in the cytoplasm during interphase and translocates into the nucleus upon mitotic entry, where it induces chromosome condensation (Figure 7).<ref name="pmid10485849" /> * In vertebrate cells, condensin II is localized in the nucleus, whereas condensin I resides in the cytoplasm during interphase (Figure 7). Chromosome condensation begins in prophase, prior to nuclear envelope breakdown, and is initially driven by condensin II. Upon nuclear envelope breakdown in prometaphase, condensin I gains access to chromatin; from that point onward, both condensin complexes function cooperatively in promoting chromosome condensation.<ref name="pmid15146063" /><ref name="pmid15572404" />

===Regulation by post-translational modifications=== 300px|thumb|Figure 8. Major targets of Cdk1-mediated phosphorylation are enriched within IDRs of the non-SMC subunits of human condensin I and II complexes Condensin subunits undergo various post-translational modifications (PTMs) in a cell cycle–dependent manner.<ref>{{cite journal | vauthors =Dekker B, Dekker J| title = Regulation of the mitotic chromosome folding machines | journal = Biochem J | volume = 479 | issue = 20 | pages = 2153–73 | year = 2022 | doi = 10.1042/BCJ20210140 | pmid =36268993| pmc = 9704520 }}</ref> Among these, phosphorylation during mitosis is the most extensively studied. The primary phosphorylation motifs targeted by Cdk1, namely S/TP sequences, tend to be enriched in the intrinsically disordered regions (IDRs) located at the termini of condensin subunits.<ref>{{cite journal | vauthors =Bazile F, St-Pierre J, D'Amours D | title = Three-step model for condensin activation during mitotic chromosome condensation | journal = Cell Cycle | volume = 9 | issue = 16 | pages = 3243–55 | year = 2010 | doi = 10.4161/cc.9.16.12620 | pmid =20703077| doi-access = free }}</ref> However, the distribution of these motifs and their functional contributions to ''in vivo'' regulation vary significantly across species. * In ''S. cerevisiae'', phosphorylation of the N-terminal region of the SMC4 subunit has been implicated in regulating the dynamics of chromatin binding.<ref>{{cite journal | vauthors = Robellet X, Thattikota Y, Wang F, Wee TL, Pascariu M, Shankar S, Bonneil É, Brown CM, D'Amours D | title = A high-sensitivity phospho-switch triggered by Cdk1 governs chromosome morphogenesis during cell division | journal = Genes Dev.| volume = 29 | issue = 4 | pages = 426–439 | year = 2015 | doi = 10.1101/gad.253294.114 | pmid =25691469| pmc = 4335297 }}</ref><ref>{{cite journal | vauthors = Thadani R, Kamenz J, Heeger S, Muñoz S, Uhlmann F | title = Cell-Cycle Regulation of Dynamic Chromosome Association of the Condensin Complex | journal = Cell Rep | volume = 23 | issue = 8 | pages = 2308–17 | year = 2018 | doi = 10.1016/j.celrep.2018.04.082 | pmid = 29791843| pmc = 5986713 }}</ref> * In ''S. pombe'', phosphorylation at the N-terminus of SMC4 is involved in controlling the nuclear translocation of condensin during mitosis.<ref name="pmid10485849" /> * In vertebrates, phosphorylation of the N-terminal region of the CAP-H subunit in condensin I contributes to the regulation of mitosis-specific chromosome loading (Figure 9, left).<ref>{{cite journal | vauthors = Tane S, Shintomi K, Kinoshita K, Tsubota Y, Yoshida MM, Nishiyama T, Hirano T | title = Cell cycle-specific loading of condensin I is regulated by the N-terminal tail of its kleisin subunit | journal = eLife| volume = 11 | article-number = e84694 | year = 2022 | doi = 10.7554/eLife.84694 | pmid = 36511239| pmc = 9797191 | doi-access = free }}</ref> Biochemical studies have shown that Cdk1-dependent phosphorylation is essential for both the DNA supercoiling activity<ref name="pmid9774278" /><ref name="pmid10428035" /> and chromosome assembly activity<ref name="pmid26075356" /> of condensin I. * In condensin II, Cdk1-mediated phosphorylation of the C-terminal region of the CAP-D3 subunit is involved in regulating the activity of the complex (Figure 9, right).<ref name="pmid21498573">{{cite journal |vauthors=Abe S, Nagasaka K, Hirayama Y, Kozuka-Hata H, Oyama M, Aoyagi Y, Obuse C, Hirota T | title = The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II | journal = Genes Dev| volume = 25 | issue = 8 | pages = 863–874 | year = 2011 | doi = 10.1101/gad.2016411 | pmid =21498573| pmc = 3078710 }}</ref><ref name="pmid25605712">{{cite journal |vauthors=Bakhrebah M, Zhang T, Mann JR, Kalitsis P, Hudson DF | title = Disruption of a conserved CAP-D3 threonine alters condensin loading on mitotic chromosomes leading to chromosome hypercondensation| journal = J Biol Chem | volume = 290 | issue = 10 | pages = 6156–6167 | year = 2015 | doi = 10.1074/jbc.M114.627109| doi-access = free| pmid =25605712| pmc = 4358255}}</ref><ref name="pmid 35983835"/><ref name="pmid38088875">{{cite journal |vauthors=Yoshida MM, Kinoshita K, Shintomi K, Aizawa Y, Hirano T | title = Regulation of condensin II by self-suppression and release mechanisms | journal = Mol Biol Cell | volume = 35 | issue = 2 | pages = ar21 | year = 2024 | doi = 10.1091/mbc.E23-10-0392 | pmid = 38088875| pmc = 10881152 }} </ref> CAP-D3 has also been identified as a substrate of protein phosphatase PP2A-B55.<ref name="pmid14653995">{{cite journal |vauthors=Yeong FM, Hombauer H, Wendt KS, Hirota T, Mudrak I, Mechtler K, Loregger T, Marchler-Bauer A, Tanaka K, Peters JM, Ogris E| title = Identification of a subunit of a novel Kleisin-beta/SMC complex as a potential substrate of protein phosphatase 2A | journal = Curr Biol| volume = 13 | issue = 23 | pages = 2058–2064 | year = 2003 | doi = 10.1016/j.cub.2003.10.032 | pmid =14653995| bibcode = 2003CBio...13.2058Y }}</ref>

In addition to Cdk1, other kinases have been implicated in condensin regulation in several organisms. For condensin I, Aurora B kinase<ref name="pmid17356064">{{cite journal |vauthors=Lipp JJ, Hirota T, Poser I, Peters JM | title = Aurora B controls the association of condensin I but not condensin II with mitotic chromosomes | journal = J Cell Sci| volume = 120 | issue = Pt 7 | pages = 1245–1255 | year = 2007 | doi = 10.1242/jcs.03425 | pmid =17356064}}</ref><ref name="pmid21540296">{{cite journal |vauthors=Nakazawa N, Mehrotra R, Ebe M, Yanagida M | title = Condensin phosphorylated by the Aurora-B-like kinase Ark1 is continuously required until telophase in a mode distinct from Top2 | journal = J Cell Sci| volume = 124 | issue = Pt 11 | pages = 1795–1807 | year = 2011 | doi = 10.1242/jcs.078733 | pmid =21540296}}</ref> and Polo-like kinase (Polo)<ref name="pmid19481522"/> have been shown to act as positive regulators, whereas Casein kinase 2 (CK2) acts as a negative regulator.<ref name="pmid17066080">{{cite journal |vauthors=Takemoto A, Kimura K, Yanagisawa J, Yokoyama S, Hanaoka F | title = Negative regulation of condensin I by CK2-mediated phosphorylation | journal = EMBO J| volume = 25 | issue = 22 | pages = 5339–5348 | year = 2006 | doi = 10.1038/sj.emboj.7601394 | pmid =17066080| pmc = 1636611 }}</ref> For condensin II, involvement of Polo<ref name="pmid25109385">{{cite journal |vauthors=Kim JH, Shim J, Ji MJ, Jung Y, Bong SM, Jang YJ, Yoon EK, Lee SJ, Kim KG, Kim YH, Lee C, Lee BI, Kim KT| title = The condensin component NCAPG2 regulates microtubule-kinetochore attachment through recruitment of Polo-like kinase 1 to kinetochores | journal = Nat Commun | volume = 5 | page = 4588 | year = 2014 | doi = 10.1038/ncomms5588 | pmid =25109385| bibcode = 2014NatCo...5.4588K }}</ref> and the spindle checkpoint kinase Mps1<ref name="pmid24934155">{{cite journal |vauthors=Kagami Y, Nihira K, Wada S, Ono M, Honda M, Yoshida K| title = Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis | journal = J. Cell Biol.| volume = 205 | issue = 6 | pages = 781–790 | year = 2014 | doi = 10.1083/jcb.201308172 | pmid =24934155| pmc = 4068140 }}</ref> has been suggested.

===Regulation by Short Linear Motifs (SLiMs)=== Recently, short amino acid sequences known as Short Linear Motifs (SLiMs) have gained attention as key regulators of condensin function. * In ''S. cerevisiae'', SLiMs in Sgo1 and Lrs4 mediate the recruitment of condensin to the pericentromeric and rDNA regions, respectively, through interactions with the CAP-G subunit.<ref name="pmid 39690240 ">{{cite journal |vauthors=Wang M, Robertson D, Zou J, Spanos C, Rappsilber J, Marston AL | title = Molecular mechanism targeting condensin for chromosome condensation. | journal =EMBO J | year = 2024 | volume = 44 | issue = 3 | pages = 705–735 | doi = 10.1038/s44318-024-00336-6 | pmid = 39690240 | pmc = 11791182 }} </ref> * In human condensin I, a SLiM-like motif located in the N-terminal region of CAP-H has been shown to play an essential role in autoinhibition of the complex.<ref name="pmid36511239">{{cite journal |vauthors=Tane S, Shintomi K, Kinoshita K, Tsubota Y, Yoshida MM, Nishiyama T, Hirano T | title = Cell cycle-specific loading of condensin I is regulated by the N-terminal tail of its kleisin subunit | journal = eLife| volume = 11 | article-number = e84694 | year = 2022 | doi = 10.7554/eLife.84694 | doi-access = free | pmid = 36511239| pmc = 9797191 }} </ref> Subsequent studies revealed that this motif, together with the C-terminal region of CAP-D2, interacts with CAP-G, and that the SLiM of the chromokinesin KIF4A competes with this interaction, thereby relieving the inhibitory constraint on condensin I activity.<ref name="pmid 39690239 ">{{cite journal |vauthors=Cutts EE, Tetiker D, Kim E, Aragon L | title = Molecular mechanism of condensin I activation by KIF4A.| journal =EMBO J | year = 2024 | volume = 44| issue = 3| pages = 682–704| doi = 10.1038/s44318-024-00340-w| pmid = 39690239| pmc = 11790958}}</ref> * In human condensin II, a SLiM in the microcephaly-associated protein MCPH1 interacts with CAP-G2, contributing to the suppression of condensin II activity in interphase.<ref name="pmid21911480" /><ref name="pmid34850993">{{cite journal |vauthors=Houlard M, Cutts EE, Shamim MS, Godwin J, Weisz D, Presser Aiden A, Lieberman Aiden E, Schermelleh L, Vannini A, Nasmyth K | title = MCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interface | journal = eLife | volume = 10 | pages = 451–469 | year = 2021 | issue = 2 | pmid = 34850993 | doi = 10.7554/eLife.73348| doi-access = free | pmc = 8673838 }}</ref> During mitosis, a SLiM in M18BP1, a subunit of the Mis18 complex involved in loading CENP-A at centromeres, competes with the SLiM of MCPH1, thereby activating condensin II.<ref name="pmid40614722">{{cite journal |vauthors=Borsellini A, Conti D, Cutts EE, Harris RJ, Walstein K, Graziadei A, Cecatiello V, Aarts TF, Xie R, Mazouzi A, Sen S, Hoencamp C, Pleuger R, Ghetti S, Oberste-Lehn L, Pan D, Bange T, Haarhuis JH, Perrakis A, Brummelkamp TR, Rowland BD, Musacchio A, Vannini A | title = Condensin II activation by M18BP1 | journal = Mol Cell | pages = S1097‑2765(25)00543‑X | year = 2025 | pmid = 40614722 | doi = 10.1016/j.molcel.2025.06.014| doi-access = free }}</ref>

These SLiM-mediated interactions are further regulated by phosphorylation of the motif itself or its surrounding regions.

===Regulation by proteolysis=== It has been reported that the CAP-H2 subunit of condensin II is degraded in ''D. melanogaster'' through the action of the SCFSlimb ubiquitin ligase.<ref name="pmid23530065">{{cite journal | vauthors =Buster DW, Daniel SG, Nguyen HQ, Windler SL, Skwarek LC, Peterson M, Roberts M, Meserve JH, Hartl T, Klebba JE, Bilder D, Bosco G, Rogers GC| title = SCFSlimb ubiquitin ligase suppresses condensin II-mediated nuclear reorganization by degrading Cap-H2 | journal = J. Cell Biol.| volume = 201 | issue = 1 | pages = 49–63 | year = 2013 | doi = 10.1083/jcb.201207183 | pmid =23530065| pmc = 3613687 }}</ref>

==Relevance to diseases== It was demonstrated that MCPH1, one of the proteins responsible for human primary microcephaly, has the ability to negatively regulate condensin II.<ref name="pmid21911480" /> In ''mcph1'' patient cells, condensin II (but not condensin I) is hyperactivated, leading to premature chromosome condensation in G2 phase (i.e., before entering mitosis).<ref>{{cite journal | vauthors = Trimborn M, Schindler D, Neitzel H, Hirano T| title = Misregulated chromosome condensation in MCPH1 primary microcephaly is mediated by condensin II| journal = Cell Cycle| volume = 5 | issue = 3 | pages = 322–6 | year = 2006 | doi = 10.4161/cc.5.3.2412| pmid = 16434882| doi-access = free}}</ref> There is no evidence, however, that misregulation of condensin II is directly related to the etiology of ''mcph1'' microcephaly. More recently, it has been reported that hypomorphic mutations in condensin I or II subunits cause microcephaly in humans.<ref>{{cite journal | vauthors =Martin CA, Murray JE, Carroll P, Leitch A, Mackenzie KJ, Halachev M, Fetit AE, Keith C, Bicknell LS, Fluteau A, Gautier P, Hall EA, Joss S, Soares G, Silva J, Bober MB, Duker A, Wise CA, Quigley AJ, Phadke SR, ((The Deciphering Developmental Disorders Study)), Wood AJ, Vagnarelli P, Jackson AP | title =Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis | journal = Genes Dev | volume = 30 | issue = 19| pages = 2158–72 | year = 2016 | doi =10.1101/gad.286351.116 | pmid = 27737959 |pmc=5088565}}</ref> In mice, hypomorphic mutations in condensin II subunits cause specific defects in T cell development,<ref name="pmid17640884">{{cite journal | vauthors = Gosling KM, Makaroff LE, Theodoratos A, Kim YH, Whittle B, Rui L, Wu H, Hong NA, Kennedy GC, Fritz JA, Yates AL, Goodnow CC, Fahrer AM| title = A mutation in a chromosome condensin II subunit, kleisin beta, specifically disrupts T cell development| journal = Proc. Natl. Acad. Sci. USA| volume = 104 |issue=30 |pages=12445–50 | year = 2007 | doi = 10.1073/pnas.0704870104| pmid = 17640884| pmc=1941488 |bibcode=2007PNAS..10412445G |doi-access=free}}</ref> leading to T cell lymphoma.<ref>{{cite journal | vauthors = Woodward J, Taylor GC, Soares DC, Boyle S, Sie D, Read D, Chathoth K, Vukovic M, Tarrats N, Jamieson D, Campbell KJ, Blyth K, Acosta JC, Ylstra B, Arends MJ, Kranc KR, Jackson AP, Bickmore WA, Wood AJ | title = Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability | journal = Genes Dev. | volume = 30 | issue = 19| pages = 2173–86 | year = 2016 | doi = 10.1101/gad.284562.116 | pmid = 27737961| pmc = 5088566}}</ref> It is interesting to note that cell types with specialized cell division modes, such as neural stem cells and T cells, are particularly susceptible to mutations in condensin subunits.

==Evolutionary implications== The presence of condensin-like complexes in prokaryotes<ref name="pmid12065423">{{cite journal |vauthors=Mascarenhas J, Soppa J, Strunnikov AV, Graumann PL | title = Cell cycle-dependent localization of two novel prokaryotic chromosome segregation and condensation proteins in Bacillus subtilis that interact with SMC protein | journal = EMBO J.| volume = 21 | issue = 12 | pages = 3108–18 | year = 2002 | doi = 10.1093/emboj/cdf314 | pmid = 12065423| pmc = 126067 }}</ref><ref name="pmid10545099">{{cite journal |vauthors=Yamazoe M, Onogi T, Sunako Y, Niki H, Yamanaka K, Ichimura T, Hiraga S | title = Complex formation of MukB, MukE and MukF proteins involved in chromosome partitioning in Escherichia coli | journal = EMBO J.| volume = 18 | issue = 21 | pages = 5873–84 | year = 1999 | doi = 10.1093/emboj/18.21.5873 | pmid = 10545099| pmc = 1171653 }}</ref> suggests that the evolutionary origin of condensins predates that of histones.

500px|thumb|Figure 9. Evolution of eukayotic condensins: SMC^c, canonical SMC; SMC^nc, non-canonical SMC; SMC¹⁴, ancestor of SMC1 & SMC4; SMC²³, ancestor of SMC2 & SMC3; SMC5⁵⁶, ancestor of SMC5 & SMC6 The proposed evolutionary scenario for eukaryotic condensins is as follows (Figure 9):<ref>{{cite journal |vauthors=Yoshinaga M, Inagaki Y | title = Ubiquity and Origins of Structural Maintenance of Chromosomes (SMC) Proteins in Eukaryotes | journal = Genome Biol Evol | volume = 13 | issue = 12 | article-number = evab256 | year = 2021 | pmid = 34894224 | doi = 10.1093/gbe/evab256| pmc = 8665677}}</ref><ref name="pmid40540396">{{cite journal |vauthors=van Hooff JJ, Raas MW, Tromer EC, Eme L |title=Repeated duplications and losses shaped SMC complex evolution from archaeal ancestors to modern eukaryotes |journal=Cell Rep |volume=44 |issue=7 |article-number=115855 |year=2025 |pmid=40540396 |doi=10.1016/j.celrep.2025.115855|doi-access=free |hdl=11370/c8ebbd65-d9db-4a2f-ac9b-dcb75b17c115 |hdl-access=free }}</ref> # In the archaeal ancestor of eukaryotes, a gene duplication event gave rise to a non-canonical SMC from a canonical SMC. This non-canonical SMC later evolved into the ancestral form of the eukaryotic SMC5/6 complex. # In the early stages of eukaryogenesis, a duplication of the canonical SMC, accompanied by the replacement of KITEs with HEATs, gave rise to the common ancestor of cohesin and condensin complexes. # A second duplication of SMC subsequently produced the distinct ancestral complexes of cohesin and condensin. # In the ancestor of condensin, a duplication of non-SMCs led to the emergence of two distinct complexes, condensin I and condensin II. # The last eukaryotic common ancestor (LECA) is thought to have possessed both condensin I and condensin II. During subsequent evolution, however, some lineages lost part or all of the non-SMC subunits specific to condensin II (see the section of Subunit composition and phylogeny).

Then how are the two condensin complexes in eukaryotic cells functionally specialized? As discussed above, the relative contribution of condensins I and II to mitosis varies among different organisms. They play equally important roles in mammalian mitosis, whereas condensin I has a predominant role over condensin II in many other species. In those species, condensin II might have been adapted for various non-essential functions other than mitosis.<ref name="pmid21917552">{{cite journal | vauthors = Sakamoto T, Inui YT, Uraguchi S, Yoshizumi T, Matsunaga S, Mastui M, Umeda M, Fukui K, Fujiwara T| title = Condensin II alleviates DNA damage and is essential for tolerance of boron overload stress in Arabidopsis| journal = Plant Cell| volume = 23 | issue = 9 | pages = 3533–46 | year = 2011 | doi = 10.1105/tpc.111.086314| pmid = 21917552| pmc = 3203421| bibcode = 2011PlanC..23.3533S}}</ref><ref name="pmid19039137">{{cite journal | vauthors = Hartl TA, Smith HF, Bosco G | title =Chromosome alignment and transvection are antagonized by condensin II. | journal = Science | volume = 322 | issue = 5906 | pages = 1384–7 | year = 2008 | pmid = 19039137 | doi=10.1126/science.1164216| bibcode =2008Sci...322.1384H | s2cid =5154197 }}</ref> Although there is no apparent relationship between the occurrence of condensin II and the size of genomes, it seems that the functional contribution of condensin II becomes big as the genome size increases.<ref name="pmid23783031">{{cite journal | vauthors = Fujiwara T, Tanaka K, Kuroiwa T, Hirano T | title = Spatiotemporal dynamics of condensins I and II: evolutionary insights from the primitive red alga Cyanidioschyzon merolae | journal = Mol. Biol. Cell | volume = 24 | issue = 16 | pages = 2515–27 | year = 2013 | doi = 10.1091/mbc.E13-04-0208 | pmid = 23783031| pmc = 3744952 }}</ref><ref name="pmid25474630">{{cite journal |vauthors=Nishide K, Hirano T| title = Overlapping and non-overlapping functions of condensins I and II in neural stem cell divisions| journal = PLOS Genet| volume = 10 | issue = 12 | article-number = e1004847| year = 2014 | doi = 10.1371/journal.pgen.1004847| doi-access = free| pmid = 25474630 | pmc = 4256295}}</ref> A recent, comprehensive Hi-C study argues from an evolutionary point of view that condensin II acts as a determinant that converts post-mitotic Rabl configurations into interphase chromosome territories.<ref>{{cite journal | vauthors = Hoencamp C, Dudchenko O, Elbatsh AM, Brahmachari S, Raaijmakers JA, van Schaik T, Sedeño Cacciatore Á, Contessoto VG, van Heesbeen RG, van den Broek B, Mhaskar AN, Teunissen H, St Hilaire BG, Weisz D, Omer AD, Pham M, Colaric Z, Yang Z, Rao SS, Mitra N, Lui C, Yao W, Khan R, Moroz LL, Kohn A, St Leger J, Mena A, Holcroft K, Gambetta MC, Lim F, Farley E, Stein N, Haddad A, Chauss D, Mutlu AS, Wang MC, Young ND, Hildebrandt E, Cheng HH, Knight CJ, Burnham TL, Hovel KA, Beel AJ, Mattei PJ, Kornberg RD, Warren WC, Cary G, Gómez-Skarmeta JL, Hinman V, Lindblad-Toh K, Di Palma F, Maeshima K, Multani AS, Pathak S, Nel-Themaat L, Behringer RR, Kaur P, Medema RH, van Steensel B, de Wit E, Onuchic JN, Di Pierro M, Lieberman Aiden E, Rowland BD| title = 3D genomics across the tree of life reveals condensin II as a determinant of architecture type| journal = Science | volume = 372 | issue = 6545 | pages = 984–9 | year = 2021 | doi = 10.1126/science.abe2218| pmid = 34045355 | pmc = 8172041}}</ref> The relative contribution of the two condensin complexes to mitotic chromosome architecture also change during development, making an impact on the morphology of mitotic chromosomes.<ref name="pmid21715560">{{cite journal | vauthors = Shintomi K, Hirano T | title =The relative ratio of condensin I to II determines chromosome shapes | journal = Genes Dev. | volume = 25 | issue = 14 | pages = 1464–9 | year = 2011 | doi =10.1101/gad.2060311 | pmid = 21715560| pmc =3143936 }}</ref> Thus, the balancing act of condensins I and II is apparently fine-tuned in both evolution and development.

== See also == * chromosome * chromosome condensation * nucleoid * mitosis * meiosis * cell cycle * cohesin * SMC protein * ATPase * HEAT repeat * Topoisomerase II * DNA supercoil

== References == {{reflist|2|refs=

<ref name="pmid21911480">{{cite journal |vauthors=Yamashita D, Shintomi K, Ono T, Gavvovidis I, Schindler D, Neitzel H, Trimborn M, Hirano T |title=MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II |journal=J. Cell Biol. |volume=194 |issue=6 |pages=841–854 |year=2011 |doi=10.1083/jcb.201106141 |pmid=21911480 |pmc=3207293}}</ref>

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==External links== {{Commons category|Condensins}} * {{MeshName|condensin}}

{{Nucleus}}

Category:Cell cycle Category:Mitosis Category:Protein complexes