NTHL1

{{cs1 config|name-list-style=vanc}} {{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Endonuclease III-like protein 1''' is an enzyme that in humans is encoded by the ''NTHL1'' gene.<ref name="pmid9045706">{{cite journal | vauthors = Hilbert TP, Chaung W, Boorstein RJ, Cunningham RP, Teebor GW | title = Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III | journal = J Biol Chem | volume = 272 | issue = 10 | pages = 6733–40 |date=Apr 1997 | pmid = 9045706 | doi =10.1074/jbc.272.10.6733 | doi-access = free }}</ref><ref name="pmid8990169">{{cite journal | vauthors = Aspinwall R, Rothwell DG, Roldan-Arjona T, Anselmino C, Ward CJ, Cheadle JP, Sampson JR, Lindahl T, Harris PC, Hickson ID | title = Cloning and characterization of a functional human homolog of Escherichia coli endonuclease III | journal = Proc Natl Acad Sci U S A | volume = 94 | issue = 1 | pages = 109–14 |date=Feb 1997 | pmid = 8990169 | pmc = 19249 | doi =10.1073/pnas.94.1.109 | bibcode = 1997PNAS...94..109A | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: NTHL1 nth endonuclease III-like 1 (E. coli)| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=4913}}</ref>

As reviewed by Li et al.,<ref name=Li>{{cite journal |vauthors=Li J, Braganza A, Sobol RW |title=Base excision repair facilitates a functional relationship between Guanine oxidation and histone demethylation |journal=Antioxid. Redox Signal. |volume=18 |issue=18 |pages=2429–43 |year=2013 |pmid=23311711 |pmc=3671628 |doi=10.1089/ars.2012.5107 }}</ref> NTHL1 is a bifunctional DNA glycosylase that has an associated beta-elimination activity. NTHL1 is usually involved in removing oxidative pyrimidine lesions through base excision repair. NTHL1 catalyses the first step in base excision repair. It cleaves the N-glycosylic bond between the damaged base and its associated sugar residue and then cleaves the phosphodiester bond 3' to the AP site,<ref name="pmid21930793">{{cite journal |vauthors=Odell ID, Barbour JE, Murphy DL, Della-Maria JA, Sweasy JB, Tomkinson AE, Wallace SS, Pederson DS |title=Nucleosome disruption by DNA ligase III-XRCC1 promotes efficient base excision repair |journal=Mol. Cell. Biol. |volume=31 |issue=22 |pages=4623–32 |year=2011 |pmid=21930793 |pmc=3209256 |doi=10.1128/MCB.05715-11 }}</ref> leaving a 3'-unsaturated aldehyde after beta-elimination and a 5'-phosphate at the termini of the repair gap.<ref name=Li />

Low expression of NTHL1 is associated with initiation and development of astrocytoma.<ref name="pmid17034947">{{cite journal |vauthors=Jiang Z, Hu J, Li X, Jiang Y, Zhou W, Lu D |title=Expression analyses of 27 DNA repair genes in astrocytoma by TaqMan low-density array |journal=Neurosci. Lett. |volume=409 |issue=2 |pages=112–7 |year=2006 |pmid=17034947 |doi=10.1016/j.neulet.2006.09.038 |s2cid=54278905 }}</ref> Low expression of NTHL1 is also found in follicular thyroid tumors.<ref name="pmid22331172">{{cite journal |vauthors=Karger S, Krause K, Engelhardt C, Weidinger C, Gimm O, Dralle H, Sheu-Grabellus SY, Schmid KW, Fuhrer D |title=Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours |journal=J. Mol. Endocrinol. |volume=48 |issue=3 |pages=193–202 |year=2012 |pmid=22331172 |doi=10.1530/JME-11-0119 |doi-access=free }}</ref>

A germ line homozygous mutation in ''NTHL1'' causes a cancer susceptibility syndrome similar to Lynch syndrome.<ref name="pmid26431160">{{cite journal |vauthors=Kuiper RP, Hoogerbrugge N |title=NTHL1 defines novel cancer syndrome |journal=Oncotarget |volume= 6|issue= 33|pages= 34069–70|year=2015 |pmid=26431160 |doi= 10.18632/oncotarget.5864|pmc=4741436}}</ref><ref name="pmid25938944">{{cite journal |vauthors=Weren RD, Ligtenberg MJ, Kets CM, de Voer RM, Verwiel ET, Spruijt L, van Zelst-Stams WA, Jongmans MC, Gilissen C, Hehir-Kwa JY, Hoischen A, Shendure J, Boyle EA, Kamping EJ, Nagtegaal ID, Tops BB, Nagengast FM, Geurts van Kessel A, van Krieken JH, Kuiper RP, Hoogerbrugge N |title=A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer |journal=Nat. Genet. |volume=47 |issue=6 |pages=668–71 |year=2015 |pmid=25938944 |doi=10.1038/ng.3287 |s2cid=24075977 }}</ref>

== See also == * OGG1 * NEIL1 * NEIL2 * NEIL3

==References== {{reflist}}

==Further reading== {{refbegin | 2}} * {{cite journal |vauthors=Hilbert TP, Boorstein RJ, Kung HC, etal |title=Purification of a mammalian homologue of Escherichia coli endonuclease III: identification of a bovine pyrimidine hydrate-thymine glycol DNAse/AP lyase by irreversible cross linking to a thymine glycol-containing oligoxynucleotide. |journal=Biochemistry |volume=35 |issue= 8 |pages= 2505–11 |year= 1996 |pmid= 8611553 |doi= 10.1021/bi952516e }} * {{cite journal |vauthors=Ikeda S, Biswas T, Roy R, etal |title=Purification and characterization of human NTH1, a homolog of Escherichia coli endonuclease III. Direct identification of Lys-212 as the active nucleophilic residue. |journal=J. Biol. Chem. |volume=273 |issue= 34 |pages= 21585–93 |year= 1998 |pmid= 9705289 |doi=10.1074/jbc.273.34.21585 |doi-access=free }} * {{cite journal |vauthors=Sarker AH, Ikeda S, Nakano H, etal |title=Cloning and characterization of a mouse homologue (mNthl1) of Escherichia coli endonuclease III. |journal=J. Mol. Biol. |volume=282 |issue= 4 |pages= 761–74 |year= 1999 |pmid= 9743625 |doi= 10.1006/jmbi.1998.2042 |s2cid=24931694 |url=https://escholarship.org/uc/item/3xp6z154 }} * {{cite journal |vauthors=Imai K, Sarker AH, Akiyama K, etal |title=Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes. |journal=Gene |volume=222 |issue= 2 |pages= 287–95 |year= 1999 |pmid= 9831664 |doi=10.1016/S0378-1119(98)00485-5 }} * {{cite journal | author=Bessho T |title=Nucleotide excision repair 3' endonuclease XPG stimulates the activity of base excision repairenzyme thymine glycol DNA glycosylase. |journal=Nucleic Acids Res. |volume=27 |issue= 4 |pages= 979–83 |year= 1999 |pmid= 9927729 |doi=10.1093/nar/27.4.979 | pmc=148276 }} * {{cite journal |vauthors=Luna L, Bjørås M, Hoff E, etal |title=Cell-cycle regulation, intracellular sorting and induced overexpression of the human NTH1 DNA glycosylase involved in removal of formamidopyrimidine residues from DNA. |journal=Mutat. Res. |volume=460 |issue= 2 |pages= 95–104 |year= 2000 |pmid= 10882850 |doi= 10.1016/s0921-8777(00)00015-x}} * {{cite journal |vauthors=Matsumoto Y, Zhang QM, Takao M, etal |title=Escherichia coli Nth and human hNTH1 DNA glycosylases are involved in removal of 8-oxoguanine from 8-oxoguanine/guanine mispairs in DNA. |journal=Nucleic Acids Res. |volume=29 |issue= 9 |pages= 1975–81 |year= 2002 |pmid= 11328882 |doi=10.1093/nar/29.9.1975 | pmc=37258 }} * {{cite journal |vauthors=Miyabe I, Zhang QM, Kino K, etal |title=Identification of 5-formyluracil DNA glycosylase activity of human hNTH1 protein. |journal=Nucleic Acids Res. |volume=30 |issue= 15 |pages= 3443–8 |year= 2002 |pmid= 12140329 |doi=10.1093/nar/gkf460 | pmc=137084 }} * {{cite journal | vauthors=Liu X, Roy R |title=Truncation of amino-terminal tail stimulates activity of human endonuclease III (hNTH1). |journal=J. Mol. Biol. |volume=321 |issue= 2 |pages= 265–76 |year= 2002 |pmid= 12144783 |doi=10.1016/S0022-2836(02)00623-X }} * {{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=Marenstein DR, Chan MK, Altamirano A, etal |title=Substrate specificity of human endonuclease III (hNTH1). Effect of human APE1 on hNTH1 activity. |journal=J. Biol. Chem. |volume=278 |issue= 11 |pages= 9005–12 |year= 2003 |pmid= 12519758 |doi= 10.1074/jbc.M212168200 |doi-access= free }} * {{cite journal | vauthors=Ikeda S, Kohmoto T, Tabata R, Seki Y |title=Differential intracellular localization of the human and mouse endonuclease III homologs and analysis of the sorting signals. |journal=DNA Repair (Amst.) |volume=1 |issue= 10 |pages= 847–54 |year= 2003 |pmid= 12531031 |doi=10.1016/S1568-7864(02)00145-3 }} * {{cite journal | vauthors=Liu X, Choudhury S, Roy R |title=In vitro and in vivo dimerization of human endonuclease III stimulates its activity. |journal=J. Biol. Chem. |volume=278 |issue= 50 |pages= 50061–9 |year= 2004 |pmid= 14522981 |doi= 10.1074/jbc.M309997200 |doi-access= free }} * {{cite journal |vauthors=Katafuchi A, Nakano T, Masaoka A, etal |title=Differential specificity of human and Escherichia coli endonuclease III and VIII homologues for oxidative base lesions. |journal=J. Biol. Chem. |volume=279 |issue= 14 |pages= 14464–71 |year= 2004 |pmid= 14734554 |doi= 10.1074/jbc.M400393200 |doi-access= free }} * {{cite journal |vauthors=Wiederhold L, Leppard JB, Kedar P, etal |title=AP endonuclease-independent DNA base excision repair in human cells. |journal=Mol. Cell |volume=15 |issue= 2 |pages= 209–20 |year= 2004 |pmid= 15260972 |doi= 10.1016/j.molcel.2004.06.003 |doi-access= free }} * {{cite journal |vauthors=Oyama M, Wakasugi M, Hama T, etal |title=Human NTH1 physically interacts with p53 and proliferating cell nuclear antigen. |journal=Biochem. Biophys. Res. Commun. |volume=321 |issue= 1 |pages= 183–91 |year= 2004 |pmid= 15358233 |doi= 10.1016/j.bbrc.2004.06.136 }} * {{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=Zhang QM, Yonekura S, Takao M, etal |title=DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the hNEIL1 and hNTH1 enzymes in human cells. |journal=DNA Repair (Amst.) |volume=4 |issue= 1 |pages= 71–9 |year= 2005 |pmid= 15533839 |doi= 10.1016/j.dnarep.2004.08.002 }} {{refend}}