NEIL1
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| Location (UCSC) | Chr 15: 75.35 – 75.36 Mb | Chr 9: 57.05 – 57.06 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Endonuclease VIII-like 1 is an enzyme that in humans is encoded by the NEIL1 gene.[5][6]
NEIL1 belongs to a class of DNA glycosylases homologous to the bacterial Fpg/Nei family. These glycosylases initiate the first step in base excision repair by cleaving bases damaged by reactive oxygen species (ROS) and introducing a DNA strand break via the associated lyase reaction.[6]
Targets
NEIL1 recognizes (targets) and removes certain ROS-damaged bases and then incises the abasic site via β,δ elimination, leaving 3′ and 5′ phosphate ends. NEIL1 recognizes oxidized pyrimidines, formamidopyrimidines, thymine residues oxidized at the methyl group, and both stereoisomers of thymine glycol.[7] The best substrates for human NEIL1 appear to be the hydantoin lesions, guanidinohydantoin, and spiroiminodihydantoin that are further oxidation products of 8-oxoG. NEIL1 is also capable of removing lesions from single-stranded DNA as well as from bubble and forked DNA structures. Because the expression of NEIL1 is cell-cycle dependent, and because it acts on forked DNA structures and interacts with PCNA and FEN-1, it has been proposed that NEIL1 functions in replication associated DNA repair.
Deficiency in cancer
NEIL1 is one of the
While other DNA repair genes, such as
DNA damage appears to be the primary underlying cause of cancer.
In colon cancer,
Memory retention
NEIL1 promotes short-term spatial memory retention. Mice lacking NEIL1 have impaired memory retention in a water maze test.[15]
Stroke prevention
NEIL1 also protects against ischemic stroke-induced brain dysfunction and death in mice.[15] NEIL1 deficiency causes brain damage and a functionally defective outcome in a mouse model of stroke.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000140398 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032298 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 11904416.
- ^ a b "Entrez Gene: NEIL1 nei endonuclease VIII-like 1 (E. coli)".
- PMID 20955798.
- PMID 22286769.
- PMID 24569633.
- ^ PMID 24811787.
- PMID 18403632.
- PMID 18704159.
- PMID 17616978.
- PMID 20420945.
- ^ PMID 22927410.
Further reading
- Takao M, Kanno S, Kobayashi K, Zhang QM, Yonei S, van der Horst GT, Yasui A (Nov 2002). "A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue". The Journal of Biological Chemistry. 277 (44): 42205–13. PMID 12200441.
- Morland I, Rolseth V, Luna L, Rognes T, Bjørås M, Seeberg E (Nov 2002). "Human DNA glycosylases of the bacterial Fpg/MutM superfamily: an alternative pathway for the repair of 8-oxoguanine and other oxidation products in DNA". Nucleic Acids Research. 30 (22): 4926–36. PMID 12433996.
- Bandaru V, Sunkara S, Wallace SS, Bond JP (Jul 2002). "A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII". DNA Repair. 1 (7): 517–29. PMID 12509226.
- Dou H, Mitra S, Hazra TK (Dec 2003). "Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2". The Journal of Biological Chemistry. 278 (50): 49679–84. PMID 14522990.
- Katafuchi A, Nakano T, Masaoka A, Terato H, Iwai S, Hanaoka F, Ide H (Apr 2004). "Differential specificity of human and Escherichia coli endonuclease III and VIII homologues for oxidative base lesions". The Journal of Biological Chemistry. 279 (14): 14464–71. PMID 14734554.
- Bandaru V, Cooper W, Wallace SS, Doublié S (Jun 2004). "Overproduction, crystallization and preliminary crystallographic analysis of a novel human DNA-repair enzyme that recognizes oxidative DNA damage". Acta Crystallographica Section D. 60 (Pt 6): 1142–4. PMID 15159582.
- Doublié S, Bandaru V, Bond JP, Wallace SS (Jul 2004). "The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity". Proceedings of the National Academy of Sciences of the United States of America. 101 (28): 10284–9. PMID 15232006.
- Wiederhold L, Leppard JB, Kedar P, Karimi-Busheri F, Rasouli-Nia A, Weinfeld M, Tomkinson AE, Izumi T, Prasad R, Wilson SH, Mitra S, Hazra TK (Jul 2004). "AP endonuclease-independent DNA base excision repair in human cells". Molecular Cell. 15 (2): 209–20. PMID 15260972.
- Shinmura K, Tao H, Goto M, Igarashi H, Taniguchi T, Maekawa M, Takezaki T, Sugimura H (Dec 2004). "Inactivating mutations of the human base excision repair gene NEIL1 in gastric cancer". Carcinogenesis. 25 (12): 2311–7. PMID 15319300.
- Mokkapati SK, Wiederhold L, Hazra TK, Mitra S (Sep 2004). "Stimulation of DNA glycosylase activity of OGG1 by NEIL1: functional collaboration between two human DNA glycosylases". Biochemistry. 43 (36): 11596–604. PMID 15350146.
- Zhang QM, Yonekura S, Takao M, Yasui A, Sugiyama H, Yonei S (Jan 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. 4 (1): 71–9. PMID 15533839.
- Das A, Hazra TK, Boldogh I, Mitra S, Bhakat KK (Oct 2005). "Induction of the human oxidized base-specific DNA glycosylase NEIL1 by reactive oxygen species". The Journal of Biological Chemistry. 280 (42): 35272–80. PMID 16118226.
- Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. S2CID 4427026.
- Ocampo-Hafalla MT, Altamirano A, Basu AK, Chan MK, Ocampo JE, Cummings A, Boorstein RJ, Cunningham RP, Teebor GW (Apr 2006). "Repair of thymine glycol by hNth1 and hNeil1 is modulated by base pairing and cis-trans epimerization". DNA Repair. 5 (4): 444–54. PMID 16446124.
- Broderick P, Bagratuni T, Vijayakrishnan J, Lubbe S, Chandler I, Houlston RS (2006). "Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition". BMC Cancer. 6: 243. PMID 17029639.
- Katafuchi A, Matsubara M, Terato H, Iwai S, Hanaoka F, Ide H (2007). "Damage specificity of human DNA glycosylases for oxidative pyrimidine lesions". Nucleic Acids Symposium Series. 48 (1): 175–6. PMID 17150535.
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