TREX2

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Three prime repair exonuclease 2''' is an enzyme that in humans is encoded by the ''TREX2'' gene.<ref name="pmid10391904">{{cite journal | vauthors = Mazur DJ, Perrino FW | title = Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'-->5' exonucleases | journal = J Biol Chem | volume = 274 | issue = 28 | pages = 19655–60 |date=Aug 1999 | pmid = 10391904 | doi =10.1074/jbc.274.28.19655 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TREX2 three prime repair exonuclease 2| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=11219}}</ref>

This gene encodes a protein with 3' exonuclease activity. Enzymes with this activity are involved in DNA replication, repair, and recombination. Similarity to an E. coli protein suggests that this enzyme may be a subunit of DNA polymerase III, which does not have intrinsic exonuclease activity.<ref name="entrez" />

Newer research has determined that ''TREX2'' is also involved in flap endonuclease activity, as detected in the context of inhibiting gene-editing nickases that generate an extension flap such as prime editors that do not usually create a double-stranded break. This function was first demonstrated in a thesis by Lung in 2021,<ref>{{Cite web |last=Lung |first=Genesis |date=Nov 2021 |title=Precise Correction of A1AT E342K by Modified NGA PAM Prime Editing and Determination of Prime Editing Inhibition by TREX2 |url=https://dash.harvard.edu/handle/1/37370046}}</ref> and replicated by Koeppel et al. in 2023.<ref>{{Cite journal |last1=Koeppel |first1=Jonas |last2=Weller |first2=Juliane |last3=Peets |first3=Elin Madli |last4=Pallaseni |first4=Ananth |last5=Kuzmin |first5=Ivan |last6=Raudvere |first6=Uku |last7=Peterson |first7=Hedi |last8=Liberante |first8=Fabio Giuseppe |last9=Parts |first9=Leopold |date=2023 |title=Prediction of prime editing insertion efficiencies using sequence features and DNA repair determinants |journal=Nature Biotechnology |volume=41 |issue=10 |pages=1444–1456 |doi=10.1038/s41587-023-01678-y |pmid=36797492 |pmc=10567557 }}</ref> Subsequently, ''TREX2'' has become incorporated into fusion enzymes for genetic engineering by multiple research groups for the purposes of reducing off-target edits which include chromosomal translocations and mismatched insertions.<ref>{{Cite journal |last1=Yin |first1=Jianhang |last2=Lu |first2=Rusen |last3=Xin |first3=Changchang |last4=Wang |first4=Yuhong |last5=Ling |first5=Xinyu |last6=Li |first6=Dong |last7=Zhang |first7=Weiwei |last8=Liu |first8=Mengzhu |last9=Xie |first9=Wutao |last10=Kong |first10=Lingyun |last11=Si |first11=Wen |last12=Wei |first12=Ping |last13=Xiao |first13=Bingbing |last14=Lee |first14=Hsiang-Ying |last15=Liu |first15=Tao |date=Mar 2022 |title=Cas9 exo-endonuclease eliminates chromosomal translocations during genome editing |journal=Nature Communications |volume=13 |issue=1 |pages=1204 |doi=10.1038/s41467-022-28900-w |pmid=35260581 |pmc=8904484 |bibcode=2022NatCo..13.1204Y }}</ref><ref>{{Cite journal |last1=Wang |first1=Yue |last2=Feng |first2=Yi-Li |last3=Liu |first3=Qian |last4=Liu |first4=Si-Cheng |last5=Huang |first5=Zhi-Cheng |date=Dec 2023 |title=TREX2 enables efficient genome disruption mediated by paired CRISPR-Cas9 nickases that generate 3′-overhanging ends |url=https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(23)00290-1 |journal=Cell Molecular Therapy |volume=34 |issue=102072}}</ref>

Mutations in this gene may lead to Aicardi-Goutieres syndrome.

==References== {{reflist}}

==Further reading== {{refbegin | 2}} *{{cite journal | vauthors=Shevelev IV, Hübscher U |title=The 3' 5' exonucleases |journal=Nat. Rev. Mol. Cell Biol. |volume=3 |issue= 5 |pages= 364–76 |year= 2002 |pmid= 11988770 |doi= 10.1038/nrm804 |s2cid=31605786 }} *{{cite journal |vauthors=Esposito T, Ciccodicola A, Flagiello L, etal |title=Expressed STSs and transcription of human Xq28 |journal=Gene |volume=187 |issue= 2 |pages= 185–91 |year= 1997 |pmid= 9099879 |doi=10.1016/S0378-1119(96)00772-X }} *{{cite journal | vauthors=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788–95 |year= 2001 |pmid= 11076863 |doi=10.1101/gr.143000 | pmc=310948 }} *{{cite journal |vauthors=Li T, Duan W, Yang H, etal |title=Identification of two proteins, S14 and UIP1, that interact with UCH37 |journal=FEBS Lett. |volume=488 |issue= 3 |pages= 201–5 |year= 2001 |pmid= 11163772 |doi=10.1016/S0014-5793(00)02436-4 |bibcode=2001FEBSL.488..201L |hdl=10536/DRO/DU:30009147 |s2cid=40717095 |hdl-access=free }} *{{cite journal |vauthors=Simpson JC, Wellenreuther R, Poustka A, etal |title=Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing |journal=EMBO Rep. |volume=1 |issue= 3 |pages= 287–92 |year= 2001 |pmid= 11256614 |doi= 10.1093/embo-reports/kvd058 | pmc=1083732 }} *{{cite journal | vauthors=Mazur DJ, Perrino FW |title=Structure and expression of the TREX1 and TREX2 3' --> 5' exonuclease genes |journal=J. Biol. Chem. |volume=276 |issue= 18 |pages= 14718–27 |year= 2001 |pmid= 11278605 |doi= 10.1074/jbc.M010051200 |doi-access= free }} *{{cite journal | vauthors=Mazur DJ, Perrino FW |title=Excision of 3' termini by the Trex1 and TREX2 3'-->5' exonucleases. Characterization of the recombinant proteins |journal=J. Biol. Chem. |volume=276 |issue= 20 |pages= 17022–9 |year= 2001 |pmid= 11279105 |doi= 10.1074/jbc.M100623200 |doi-access= free }} *{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }} *{{cite journal | vauthors=Shevelev IV, Beliakova NV, Kravetskaia TP, Krutiakov VM |title=[The correcting role of autonomous 3'-->5' exonucleases in mammalian multienzyme DNA polymerase complexes] |journal=Mol. Biol. (Mosk.) |volume=36 |issue= 6 |pages= 1055–61 |year= 2003 |pmid= 12500544 }} *{{cite journal | vauthors=Shevelev IV, Ramadan K, Hübscher U |title=The TREX2 3'-->5' exonuclease physically interacts with DNA polymerase delta and increases its accuracy |journal=ScientificWorldJournal |volume=2 |pages= 275–81 |year= 2004 |pmid= 12806015 |pmc=6009725 |doi= 10.1100/tsw.2002.99 |doi-access=free }} *{{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }} *{{cite journal |vauthors=Wiemann S, Arlt D, Huber W, etal |title=From ORFeome to biology: a functional genomics pipeline |journal=Genome Res. |volume=14 |issue= 10B |pages= 2136–44 |year= 2004 |pmid= 15489336 |doi= 10.1101/gr.2576704 | pmc=528930 }} *{{cite journal |vauthors=Perrino FW, Krol A, Harvey S, etal |title=Sequence variants in the 3'-->5' deoxyribonuclease TREX2: identification in a genetic screen and effects on catalysis by the recombinant proteins |journal=Adv. Enzyme Regul. |volume=44 |pages= 37–49 |year= 2005 |pmid= 15581481 |doi= 10.1016/j.advenzreg.2003.11.010 }} *{{cite journal | vauthors=Perrino FW, Harvey S, McMillin S, Hollis T |title=The human TREX2 3' -> 5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis |journal=J. Biol. Chem. |volume=280 |issue= 15 |pages= 15212–8 |year= 2005 |pmid= 15661738 |doi= 10.1074/jbc.M500108200 |doi-access= free }} *{{cite journal |vauthors=Rual JF, Venkatesan K, Hao T, etal |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 |bibcode=2005Natur.437.1173R |s2cid=4427026 }} *{{cite journal |vauthors=Mehrle A, Rosenfelder H, Schupp I, etal |title=The LIFEdb database in 2006 |journal=Nucleic Acids Res. |volume=34 |issue= Database issue |pages= D415–8 |year= 2006 |pmid= 16381901 |doi= 10.1093/nar/gkj139 | pmc=1347501 }} *{{cite journal | vauthors=Hahn Y, Lee B |title=Human-specific nonsense mutations identified by genome sequence comparisons |journal=Hum. Genet. |volume=119 |issue= 1–2 |pages= 169–78 |year= 2007 |pmid= 16395595 |doi= 10.1007/s00439-005-0125-6 |s2cid=21059468 |url=https://zenodo.org/record/1232721 }} *{{cite journal | vauthors=Chen MJ, Ma SM, Dumitrache LC, Hasty P |title=Biochemical and cellular characteristics of the 3' -> 5' exonuclease TREX2 |journal=Nucleic Acids Res. |volume=35 |issue= 8 |pages= 2682–94 |year= 2007 |pmid= 17426129 |doi= 10.1093/nar/gkm151 | pmc=1885668 }} *{{cite journal | vauthors=Parra D, Manils J, Castellana B, Viña-Vilaseca A, Morán-Salvador E, Vázquez-Villoldo N, Tarancón G, Borràs M, Sancho S, Benito C, Ortega S, and Soler C |title=Increased Susceptibility to Skin Carcinogenesis in TREX2 Knockout Mice|journal=Cancer Research |volume=69 |issue= 16 |pages= 6676–84|year= 2009 |pmid= 19654293 |doi= 10.1158/0008-5472.CAN-09-1208 |doi-access= free }} {{refend}}

== External links == * {{PDBe-KB2|Q9BQ50|Human Three prime repair exonuclease 2}} * {{PDBe-KB2|Q9R1A9|Mouse Three prime repair exonuclease 2}}