Endonuclease III-like protein 1 is an enzyme that in humans is encoded by the NTHL1gene.[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]
^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. PMID17034947. S2CID54278905.
^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. PMID25938944. S2CID24075977.
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. PMID8611553.
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. PMID9831664.
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. PMID10882850.
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. PMID12144783.
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. PMID12531031.
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. PMID15533839.