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词条 NEIL1
释义

  1. Targets

  2. Deficiency in cancer

  3. Memory retention

  4. Stroke prevention

  5. References

  6. Further reading

{{Infobox_gene}}Endonuclease VIII-like 1 is an enzyme that in humans is encoded by the NEIL1 gene.[1][2]

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.[2]

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.[3] 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 DNA repair genes most frequently hypermethylated in head and neck squamous cell carcinoma (HNSCC).[4] When 160 human DNA repair genes were evaluated for aberrant methylation in HNSCC tumors, 62% of tumors were hypermethylated in the NEIL1 promoter region, causing NEIL1 messenger RNA and NEIL1 protein to be repressed. When 8 DNA repair genes were evaluated in non-small cell lung cancer (NSCLC) tumors,[5] 42% were hypermethylated in the NEIL1 promoter region. This was the most frequent DNA repair deficiency found among the 8 DNA repair genes tested. NEIL1 was also one of six DNA repair genes found to be hypermethylated in their promoter regions in colorectal cancer.[6]

While other DNA repair genes, such as MGMT and MLH1, are often evaluated for epigenetic repression in many types of cancer,[7] epigenetic deficiency of NEIL1 is usually not evaluated, but might be of importance in such cancers as well.

DNA damage appears to be the primary underlying cause of cancer.[7][8] If DNA repair is deficient, DNA damage tends to accumulate. Such excess DNA damage may increase mutational errors during DNA replication due to error-prone translesion synthesis. Excess DNA damage may also increase epigenetic alterations due to errors during DNA repair.[9][10] Such mutations and epigenetic alterations may give rise to cancer (see malignant neoplasms).

In colon cancer, germ line mutations in DNA repair genes cause only 2–5% of cases.[11] However, methylation of the promoter region of DNA repair genes (including NEIL1[6]), are frequently associated with colon cancers and may be an important causal factor for these cancers.[7]

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Memory retention

NEIL1 promotes short-term spatial memory retention. Mice lacking NEIL1 have impaired memory retention in a water maze test.[12]

Stroke prevention

NEIL1 also protects against ischemic stroke-induced brain dysfunction and death in mice.[12] NEIL1 deficiency causes brain damage and a functionally defective outcome in a mouse model of stroke.

References

1. ^{{cite journal | vauthors = Hazra TK, Izumi T, Boldogh I, Imhoff B, Kow YW, Jaruga P, Dizdaroglu M, Mitra S | title = Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 6 | pages = 3523–8 | date = Mar 2002 | pmid = 11904416 | pmc = 122556 | doi = 10.1073/pnas.062053799 }}
2. ^1 {{cite web | title = Entrez Gene: NEIL1 nei endonuclease VIII-like 1 (E. coli)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=79661| accessdate = }}
3. ^{{cite journal | vauthors = Nemec AA, Wallace SS, Sweasy JB | title = Variant base excision repair proteins: contributors to genomic instability | journal = Seminars in Cancer Biology | volume = 20 | issue = 5 | pages = 320–8 | date = Oct 2010 | pmid = 20955798 | pmc = 3254599 | doi = 10.1016/j.semcancer.2010.10.010 }}
4. ^{{cite journal | vauthors = Chaisaingmongkol J, Popanda O, Warta R, Dyckhoff G, Herpel E, Geiselhart L, Claus R, Lasitschka F, Campos B, Oakes CC, Bermejo JL, Herold-Mende C, Plass C, Schmezer P | title = Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma | journal = Oncogene | volume = 31 | issue = 49 | pages = 5108–16 | date = Dec 2012 | pmid = 22286769 | doi = 10.1038/onc.2011.660 }}
5. ^{{cite journal | vauthors = Do H, Wong NC, Murone C, John T, Solomon B, Mitchell PL, Dobrovic A | title = A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma | journal = Scientific Reports | volume = 4 | issue = | pages = 4186 | year = 2014 | pmid = 24569633 | pmc = 3935198 | doi = 10.1038/srep04186 }}
6. ^1 {{cite journal | vauthors = Farkas SA, Vymetalkova V, Vodickova L, Vodicka P, Nilsson TK | title = DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/β-catenin signaling pathway genes | journal = Epigenomics | volume = 6 | issue = 2 | pages = 179–91 | date = Apr 2014 | pmid = 24811787 | doi = 10.2217/epi.14.7 }}
7. ^1 2 {{cite book | chapter = DNA Damage, DNA Repair and Cancer | vauthors = Bernstein C, Prasad AR, Nfonsam V, Bernstein H | year = 2013 | title = New Research Directions in DNA Repair | veditors = Chen C | isbn = 978-953-51-1114-6 | publisher = InTech | chapter-url = http://www.intechopen.com/books/new-research-directions-in-dna-repair/dna-damage-dna-repair-and-cancer | doi = 10.5772/53919 }}
8. ^{{vcite2 journal |vauthors=Kastan MB |title=DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture |journal=Mol. Cancer Res. |volume=6 |issue=4 |pages=517–24 |year=2008 |pmid=18403632 |doi=10.1158/1541-7786.MCR-08-0020 |url=}}
9. ^{{cite journal | vauthors = O'Hagan HM, Mohammad HP, Baylin SB | title = Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island | journal = PLoS Genetics | volume = 4 | issue = 8 | pages = e1000155 | year = 2008 | pmid = 18704159 | pmc = 2491723 | doi = 10.1371/journal.pgen.1000155 }}
10. ^{{cite journal | vauthors = Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV | title = DNA damage, homology-directed repair, and DNA methylation | journal = PLoS Genetics | volume = 3 | issue = 7 | pages = e110 | date = Jul 2007 | pmid = 17616978 | pmc = 1913100 | doi = 10.1371/journal.pgen.0030110 }}
11. ^{{cite journal | vauthors = Jasperson KW, Tuohy TM, Neklason DW, Burt RW | title = Hereditary and familial colon cancer | journal = Gastroenterology | volume = 138 | issue = 6 | pages = 2044–58 | date = Jun 2010 | pmid = 20420945 | doi = 10.1053/j.gastro.2010.01.054 | pmc=3057468}}
12. ^1 {{cite journal |vauthors=Canugovi C, Yoon JS, Feldman NH, Croteau DL, Mattson MP, Bohr VA |title=Endonuclease VIII-like 1 (NEIL1) promotes short-term spatial memory retention and protects from ischemic stroke-induced brain dysfunction and death in mice |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=109 |issue=37 |pages=14948–53 |date=September 2012 |pmid=22927410 |pmc=3443144 |doi=10.1073/pnas.1204156109 |url=}}

Further reading

{{refbegin|33em}}
  • {{cite journal | vauthors = Takao M, Kanno S, Kobayashi K, Zhang QM, Yonei S, van der Horst GT, Yasui A | title = A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue | journal = The Journal of Biological Chemistry | volume = 277 | issue = 44 | pages = 42205–13 | date = Nov 2002 | pmid = 12200441 | doi = 10.1074/jbc.M206884200 }}
  • {{cite journal | vauthors = Morland I, Rolseth V, Luna L, Rognes T, Bjørås M, Seeberg E | title = Human DNA glycosylases of the bacterial Fpg/MutM superfamily: an alternative pathway for the repair of 8-oxoguanine and other oxidation products in DNA | journal = Nucleic Acids Research | volume = 30 | issue = 22 | pages = 4926–36 | date = Nov 2002 | pmid = 12433996 | pmc = 137166 | doi = 10.1093/nar/gkf618 }}
  • {{cite journal | vauthors = Bandaru V, Sunkara S, Wallace SS, Bond JP | title = A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII | journal = DNA Repair | volume = 1 | issue = 7 | pages = 517–29 | date = Jul 2002 | pmid = 12509226 | doi = 10.1016/S1568-7864(02)00036-8 }}
  • {{cite journal | vauthors = Dou H, Mitra S, Hazra TK | title = Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 50 | pages = 49679–84 | date = Dec 2003 | pmid = 14522990 | doi = 10.1074/jbc.M308658200 }}
  • {{cite journal | vauthors = Katafuchi A, Nakano T, Masaoka A, Terato H, Iwai S, Hanaoka F, Ide H | title = Differential specificity of human and Escherichia coli endonuclease III and VIII homologues for oxidative base lesions | journal = The Journal of Biological Chemistry | volume = 279 | issue = 14 | pages = 14464–71 | date = Apr 2004 | pmid = 14734554 | doi = 10.1074/jbc.M400393200 }}
  • {{cite journal | vauthors = Bandaru V, Cooper W, Wallace SS, Doublié S | title = Overproduction, crystallization and preliminary crystallographic analysis of a novel human DNA-repair enzyme that recognizes oxidative DNA damage | journal = Acta Crystallographica Section D | volume = 60 | issue = Pt 6 | pages = 1142–4 | date = Jun 2004 | pmid = 15159582 | doi = 10.1107/S0907444904007929 }}
  • {{cite journal | vauthors = Doublié S, Bandaru V, Bond JP, Wallace SS | title = The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 28 | pages = 10284–9 | date = Jul 2004 | pmid = 15232006 | pmc = 478564 | doi = 10.1073/pnas.0402051101 }}
  • {{cite journal | vauthors = 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 | title = AP endonuclease-independent DNA base excision repair in human cells | journal = Molecular Cell | volume = 15 | issue = 2 | pages = 209–20 | date = Jul 2004 | pmid = 15260972 | doi = 10.1016/j.molcel.2004.06.003 }}
  • {{cite journal | vauthors = Shinmura K, Tao H, Goto M, Igarashi H, Taniguchi T, Maekawa M, Takezaki T, Sugimura H | title = Inactivating mutations of the human base excision repair gene NEIL1 in gastric cancer | journal = Carcinogenesis | volume = 25 | issue = 12 | pages = 2311–7 | date = Dec 2004 | pmid = 15319300 | doi = 10.1093/carcin/bgh267 }}
  • {{cite journal | vauthors = Mokkapati SK, Wiederhold L, Hazra TK, Mitra S | title = Stimulation of DNA glycosylase activity of OGG1 by NEIL1: functional collaboration between two human DNA glycosylases | journal = Biochemistry | volume = 43 | issue = 36 | pages = 11596–604 | date = Sep 2004 | pmid = 15350146 | doi = 10.1021/bi049097i }}
  • {{cite journal | vauthors = Zhang QM, Yonekura S, Takao M, Yasui A, Sugiyama H, Yonei S | 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 | volume = 4 | issue = 1 | pages = 71–9 | date = Jan 2005 | pmid = 15533839 | doi = 10.1016/j.dnarep.2004.08.002 }}
  • {{cite journal | vauthors = Das A, Hazra TK, Boldogh I, Mitra S, Bhakat KK | title = Induction of the human oxidized base-specific DNA glycosylase NEIL1 by reactive oxygen species | journal = The Journal of Biological Chemistry | volume = 280 | issue = 42 | pages = 35272–80 | date = Oct 2005 | pmid = 16118226 | doi = 10.1074/jbc.M505526200 }}
  • {{cite journal | vauthors = 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 | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = Oct 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
  • {{cite journal | vauthors = Ocampo-Hafalla MT, Altamirano A, Basu AK, Chan MK, Ocampo JE, Cummings A, Boorstein RJ, Cunningham RP, Teebor GW | title = Repair of thymine glycol by hNth1 and hNeil1 is modulated by base pairing and cis-trans epimerization | journal = DNA Repair | volume = 5 | issue = 4 | pages = 444–54 | date = Apr 2006 | pmid = 16446124 | doi = 10.1016/j.dnarep.2005.12.004 }}
  • {{cite journal | vauthors = Broderick P, Bagratuni T, Vijayakrishnan J, Lubbe S, Chandler I, Houlston RS | title = Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition | journal = BMC Cancer | volume = 6 | issue = | pages = 243 | year = 2006 | pmid = 17029639 | pmc = 1624846 | doi = 10.1186/1471-2407-6-243 }}
  • {{cite journal | vauthors = Katafuchi A, Matsubara M, Terato H, Iwai S, Hanaoka F, Ide H | title = Damage specificity of human DNA glycosylases for oxidative pyrimidine lesions | journal = Nucleic Acids Symposium Series | volume = 48 | issue = 1 | pages = 175–6 | year = 2007 | pmid = 17150535 | doi = 10.1093/nass/48.1.175 }}
{{refend}}{{PDB Gallery|geneid=79661}}

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