NTHL1

NTHL1
Identifiers
Aliases	NTHL1 , NTH1, OCTS3, hNTH1, FAP3, nth-like DNA glycosylase 1, nth like DNA glycosylase 1
External IDs	OMIM: 602656; MGI: 1313275; HomoloGene: 1897; GeneCards: NTHL1; OMA:NTHL1 - orthologs
Gene location (Human) Chr. Chromosome 16 (human) [1] Band 16p13.3 Start 2,039,815 bp [1] End 2,047,866 bp [1]
Gene location (Mouse) Chr. Chromosome 17 (mouse) [2] Band 17|17 A3.3 Start 24,851,654 bp [2] End 24,857,811 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver apex of heart mucosa of transverse colon right uterine tube putamen right hemisphere of cerebellum gonad nucleus accumbens caudate nucleus right frontal lobe Top expressed in blastocyst embryo zygote morula embryo primary oocyte yolk sac epiblast secondary oocyte right kidney More reference expression data BioGPS More reference expression data
Gene ontology Molecular function lyase activity protein binding catalytic activity endonuclease activity double-stranded DNA binding hydrolase activity, acting on glycosyl bonds hydrolase activity DNA binding iron-sulfur cluster binding metal ion binding 4 iron, 4 sulfur cluster binding DNA N-glycosylase activity DNA-(apurinic or apyrimidinic site) endonuclease activity oxidized purine nucleobase lesion DNA N-glycosylase activity oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity class I DNA-(apurinic or apyrimidinic site) endonuclease activity Cellular component nucleoplasm nucleus mitochondrion Biological process depyrimidination cellular response to DNA damage stimulus metabolism nucleotide-excision repair, DNA incision, 5'-to lesion DNA repair base-excision repair base-excision repair, AP site formation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4913 18207 Ensembl ENSG00000065057 ENSMUSG00000041429 UniProt P78549 O35980 RefSeq (mRNA) NM_002528 NM_001318193 NM_001318194 NM_008743 NM_001357615 RefSeq (protein) NP_001305122 NP_001305123 NP_002519 NP_032769 NP_001344544 Location (UCSC) Chr 16: 2.04 – 2.05 Mb Chr 17: 24.85 – 24.86 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Endonuclease III-like protein 1 is an enzyme that in humans is encoded by the NTHL1 gene. ^{[5] [6] [7]}

As reviewed by Li et al., ^[8] 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, ^[9] leaving a 3'-unsaturated aldehyde after beta-elimination and a 5'-phosphate at the termini of the repair gap. ^[8]

Low expression of NTHL1 is associated with initiation and development of astrocytoma. ^[10] Low expression of NTHL1 is also found in follicular thyroid tumors. ^[11]

A germ line homozygous mutation in NTHL1 causes a cancer susceptibility syndrome similar to Lynch syndrome. ^{[12] [13]}

See also

• OGG1
• NEIL1
• NEIL2
• NEIL3

References

1. GRCh38: Ensembl release 89: ENSG00000065057 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000041429 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hilbert TP, Chaung W, Boorstein RJ, Cunningham RP, Teebor GW (Apr 1997). "Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III". J Biol Chem. 272 (10): 6733–40. doi: 10.1074/jbc.272.10.6733 . PMID   9045706.
6. Aspinwall R, Rothwell DG, Roldan-Arjona T, Anselmino C, Ward CJ, Cheadle JP, Sampson JR, Lindahl T, Harris PC, Hickson ID (Feb 1997). "Cloning and characterization of a functional human homolog of Escherichia coli endonuclease III". Proc Natl Acad Sci U S A. 94 (1): 109–14. Bibcode:1997PNAS...94..109A. doi: 10.1073/pnas.94.1.109 . PMC   19249 . PMID   8990169.
7. "Entrez Gene: NTHL1 nth endonuclease III-like 1 (E. coli)".
8. Li J, Braganza A, Sobol RW (2013). "Base excision repair facilitates a functional relationship between Guanine oxidation and histone demethylation". Antioxid. Redox Signal. 18 (18): 2429–43. doi:10.1089/ars.2012.5107. PMC   3671628 . PMID   23311711.
9. Odell ID, Barbour JE, Murphy DL, Della-Maria JA, Sweasy JB, Tomkinson AE, Wallace SS, Pederson DS (2011). "Nucleosome disruption by DNA ligase III-XRCC1 promotes efficient base excision repair". Mol. Cell. Biol. 31 (22): 4623–32. doi:10.1128/MCB.05715-11. PMC   3209256 . PMID   21930793.
10. Jiang Z, Hu J, Li X, Jiang Y, Zhou W, Lu D (2006). "Expression analyses of 27 DNA repair genes in astrocytoma by TaqMan low-density array". Neurosci. Lett. 409 (2): 112–7. doi:10.1016/j.neulet.2006.09.038. PMID   17034947. S2CID   54278905.
11. Karger S, Krause K, Engelhardt C, Weidinger C, Gimm O, Dralle H, Sheu-Grabellus SY, Schmid KW, Fuhrer D (2012). "Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours". J. Mol. Endocrinol. 48 (3): 193–202. doi: 10.1530/JME-11-0119 . PMID   22331172.
12. Kuiper RP, Hoogerbrugge N (2015). "NTHL1 defines novel cancer syndrome". Oncotarget. 6 (33): 34069–70. doi:10.18632/oncotarget.5864. PMC   4741436 . PMID   26431160.
13. 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 (2015). "A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer". Nat. Genet. 47 (6): 668–71. doi:10.1038/ng.3287. PMID   25938944. S2CID   24075977.

Further reading

• Hilbert TP, Boorstein RJ, Kung HC, et al. (1996). "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". Biochemistry. 35 (8): 2505–11. doi:10.1021/bi952516e. PMID   8611553.
• Ikeda S, Biswas T, Roy R, et al. (1998). "Purification and characterization of human NTH1, a homolog of Escherichia coli endonuclease III. Direct identification of Lys-212 as the active nucleophilic residue". J. Biol. Chem. 273 (34): 21585–93. doi: 10.1074/jbc.273.34.21585 . PMID   9705289.
• Sarker AH, Ikeda S, Nakano H, et al. (1999). "Cloning and characterization of a mouse homologue (mNthl1) of Escherichia coli endonuclease III". J. Mol. Biol. 282 (4): 761–74. doi:10.1006/jmbi.1998.2042. PMID   9743625. S2CID   24931694.
• Imai K, Sarker AH, Akiyama K, et al. (1999). "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". Gene. 222 (2): 287–95. doi:10.1016/S0378-1119(98)00485-5. PMID   9831664.
• Bessho T (1999). "Nucleotide excision repair 3' endonuclease XPG stimulates the activity of base excision repairenzyme thymine glycol DNA glycosylase". Nucleic Acids Res. 27 (4): 979–83. doi:10.1093/nar/27.4.979. PMC   148276 . PMID   9927729.
• Luna L, Bjørås M, Hoff E, et al. (2000). "Cell-cycle regulation, intracellular sorting and induced overexpression of the human NTH1 DNA glycosylase involved in removal of formamidopyrimidine residues from DNA". Mutat. Res. 460 (2): 95–104. doi:10.1016/s0921-8777(00)00015-x. PMID   10882850.
• Matsumoto Y, Zhang QM, Takao M, et al. (2002). "Escherichia coli Nth and human hNTH1 DNA glycosylases are involved in removal of 8-oxoguanine from 8-oxoguanine/guanine mispairs in DNA". Nucleic Acids Res. 29 (9): 1975–81. doi:10.1093/nar/29.9.1975. PMC   37258 . PMID   11328882.
• Miyabe I, Zhang QM, Kino K, et al. (2002). "Identification of 5-formyluracil DNA glycosylase activity of human hNTH1 protein". Nucleic Acids Res. 30 (15): 3443–8. doi:10.1093/nar/gkf460. PMC   137084 . PMID   12140329.
• Liu X, Roy R (2002). "Truncation of amino-terminal tail stimulates activity of human endonuclease III (hNTH1)". J. Mol. Biol. 321 (2): 265–76. doi:10.1016/S0022-2836(02)00623-X. PMID   12144783.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Marenstein DR, Chan MK, Altamirano A, et al. (2003). "Substrate specificity of human endonuclease III (hNTH1). Effect of human APE1 on hNTH1 activity". J. Biol. Chem. 278 (11): 9005–12. doi: 10.1074/jbc.M212168200 . PMID   12519758.
• Ikeda S, Kohmoto T, Tabata R, Seki Y (2003). "Differential intracellular localization of the human and mouse endonuclease III homologs and analysis of the sorting signals". DNA Repair (Amst.). 1 (10): 847–54. doi:10.1016/S1568-7864(02)00145-3. PMID   12531031.
• Liu X, Choudhury S, Roy R (2004). "In vitro and in vivo dimerization of human endonuclease III stimulates its activity". J. Biol. Chem. 278 (50): 50061–9. doi: 10.1074/jbc.M309997200 . PMID   14522981.
• Katafuchi A, Nakano T, Masaoka A, et al. (2004). "Differential specificity of human and Escherichia coli endonuclease III and VIII homologues for oxidative base lesions". J. Biol. Chem. 279 (14): 14464–71. doi: 10.1074/jbc.M400393200 . PMID   14734554.
• Wiederhold L, Leppard JB, Kedar P, et al. (2004). "AP endonuclease-independent DNA base excision repair in human cells". Mol. Cell. 15 (2): 209–20. doi: 10.1016/j.molcel.2004.06.003 . PMID   15260972.
• Oyama M, Wakasugi M, Hama T, et al. (2004). "Human NTH1 physically interacts with p53 and proliferating cell nuclear antigen". Biochem. Biophys. Res. Commun. 321 (1): 183–91. doi:10.1016/j.bbrc.2004.06.136. PMID   15358233.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Zhang QM, Yonekura S, Takao M, et al. (2005). "DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the hNEIL1 and hNTH1 enzymes in human cells". DNA Repair (Amst.). 4 (1): 71–9. doi:10.1016/j.dnarep.2004.08.002. PMID   15533839.