The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death

Rosenquist, Thomas A.; Zaika, Elena; Fernandes, Andrea; Zharkov, Dmitry O.; Miller, Holly; Grollman, Arthur P.

doi:10.1016/s1568-7864(03)00025-9

Cited by 173 publications

(148 citation statements)

References 59 publications

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“…26,27 Cell lines lacking NEIL1 were more sensitive to g-irradiation, interstrand crosslinks and bulky adducts. 28,29 NEIL1 knockout mice showed increased levels of DNA damage, deletions and metabolic syndrome. 30 NEIL1 and NEIL1/NTH1 double knockout mice developed pulmonary and hepatocellular tumors.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma

et al. 2012

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Aberrant promoter methylation of different DNA repair genes has a critical role in the development and progression of various cancer types, including head and neck squamous cell carcinomas (HNSCCs). A systematic analysis of known human repair genes for promoter methylation is however missing. We generated quantitative promoter methylation profiles in single CpG units of 160 human DNA repair genes in a set of DNAs isolated from fresh frozen HNSCC and normal tissues using MassARRAY technology. Ninety-eight percent of these genes contained CpG islands (CGIs) in their promoter region; thus, DNA methylation is a potential regulatory mechanism. Methylation data were obtained for 145 genes, from which 15 genes exhibited more than a 20% difference in methylation levels between tumor and normal tissues, manifested either as hypermethylation or as hypomethylation. Analyses of promoter methylation with mRNA expression identified the DNA glycosylase NEIL1 (nei endonuclease VIII-like 1) as the most prominent candidate gene. NEIL1 promoter hypermethylation was confirmed in additional fresh frozen HNSCC samples, normal mucosa, HNSCC cell lines and primary human skin keratinocytes. The investigation of laser-microdissected tissues further substantiated increased methylation levels in tumor versus matched non-tumor cells. Immunohistological analysis revealed significantly less NEIL1 protein expression in tumor tissues. 5-Aza-2 0 -deoxycytidine treatment and DNMT1 knockdown resulted in the re-expression of NEIL1 in HNSCC cell lines, which initially carried hypermethylated promoter regions. In conclusion, our results suggest that DNA methylation contributes to the downregulation of NEIL1 expression and might thus have a role in modulating the response to therapies of HNSCC.

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Section: Discussionmentioning

confidence: 99%

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma

et al. 2012

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“…Nucleus, mitochondria; mouse NTH1 primarily mitochondria [Luna et al, 2000;Ikeda et al, 2002] Heart, brain [Imai et al, 1998;Karahalil et al, 2002;Rolseth et al, 2008] 5-OHU, FapyG, Tg [Aspinwall et al, 1997;Dizdaroglu et al, 1999;Rosenquist et al, 2003] MUTY Nucleus, mitochondria [Ichinoe et al, 2004] Small intestine, thymus, heart, lung, cerebellum [Ichinoe et al, 2004] Mispaired A opposite 8-oxoG; 2-OHA opposite G [Ushijima et al, 2005;Mazzei et al, 2013] The tissue distribution, intracellular localization, and major known substrates of selected BER glycosylases involved in repair of oxidative DNA lesions are presented. 2-OHA, 2-hydroxyadenine; 5-OHU, 5-hydroxyuracil; 8-oxoG, 8-hydroxyguanine; Fapy, formamidopyrimidine; Gh, guanidinohydantoin; Sp, spiroiminodihydantoin; Tg, thymine glycol.…”

Section: Nth1mentioning

confidence: 99%

“…In human studies, inactivating mutations of NEIL1 have been associated with gastric cancers [Shinmura et al, 2004]. Furthermore, cell culture studies have indicated that knock down of Neil1 renders cells more sensitive to oxidative stress, such as that induced by glucose oxidase or gamma irradiation [Rosenquist et al, 2003;Maiti et al, 2008]. NEIL1-deficient mice, although initially expected to display a promutagenic phenotype, have not been found to be significantly prone to spontaneous tumor formation, although lung adenomas and hepatocellular carcinomas have been documented in about 10-20% of aged animals [Chan et al, 2009].…”

Section: Actions Of Ber Glycosylases In Disease States Obesity and Mementioning

confidence: 99%

Oxidative DNA damage in disease—Insights gained from base excision repair glycosylase‐deficient mouse models

Sampath

2014

Environ and Mol Mutagen

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Cellular components, including nucleic acids, are subject to oxidative damage. If left unrepaired, this damage can lead to multiple adverse cellular outcomes, including increased mutagenesis and cell death. The major pathway for repair of oxidative base lesions is the base excision repair pathway, catalyzed by DNA glycosylases with overlapping but distinct substrate specificities. To understand the role of these glycosylases in the initiation and progression of disease, several transgenic mouse models have been generated to carry a targeted deletion or overexpression of one or more glycosylases. This review summarizes some of the major findings from transgenic animal models of altered DNA glycosylase expression, especially as they relate to pathologies ranging from metabolic disease and cancer to inflammation and neuronal health. Environ. Mol. Mutagen. 55:689-703, 2014. V C 2014 Wiley Periodicals, Inc.

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“…The mutant frequency is multiplied by the ratio of A:T --> C:G transversion shown in Table 4. 2 (5) >3 bases 10 (22) 18 (38) 16 ( (65) 34 (72) 33 (70) 39 (85) 29 (62) 32 ( (100) 8-oxo-dGTP Table 4. Spectra of mutations induced by 8-oxo-dGTP in 293T cells with knocked-down DNA glycosylases (continued)…”

Section: Conflict Of Interestmentioning

confidence: 99%

“…It has been reported that the overexpression of OGG1 and MUTYH suppress mutations by 8-oxo-Gua in cultured cells [30,31]. The NTH1 and NEIL1 proteins are homologues of Escherichia coli Nth and Nei, DNA glycosylases that are specific for oxidized pyrimidine bases [32][33][34][35][36][37][38][39]. The observation that NTH1 can be efficiently trapped to an oligonucleotide duplex containing 8-oxo-Gua:C by treatment with NaBH 4 , suggests that NTH1 binds to 8-oxo-Gua:C DNA [40].…”

Section: Introductionmentioning

confidence: 99%

Effects of base excision repair proteins on mutagenesis by 8-oxo-7,8-dihydroguanine (8-hydroxyguanine) paired with cytosine and adenine

2010

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, also known as 8-hydroxyguanine) is a major base lesion that is generated by reactive oxygen species in both the DNA and nucleotide pool. The role of DNA glycosylases, which initiate base excision repair, in the mutagenic processes of 8-oxo-Gua in DNA and 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP, also known as 8-hydroxy-2'-deoxyguanosine 5'-triphosphate) were investigated using supF shuttle plasmids propagated in human cells. The DNA glycosylases, OGG1, MUTYH, NTH1, and NEIL1, in 293T cells were individually knocked-down by siRNAs and plasmid DNAs containing an 8-oxo-Gua:C/8-oxo-Gua:A pair, and 8-oxo-dGTP plus unmodified plasmid DNA were then introduced into the knocked-down cells. The knock-down of OGG1, MUTYH, NTH1, and NEIL1 resulted in a significant increase in G:C → T:A transversions caused by the 8-oxo-Gua:C pair in the shuttle plasmid. The knock-down of MUTYH resulted in a reduction in A:T → C:G transversions induced by 8-oxo-dGTP and the 8-oxo-Gua:A pair, but the knockdown of OGG1, NTH1, and NEIL1 had no effect on mutagenesis. These results indicate that all of the above DNA glycosylases suppress mutations caused by 8-oxo-Gua:C in DNA. In contrast, it appears that MUTYH enhances A:T → C:G mutations caused by 8-oxo-dGTP.

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The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death

Cited by 173 publications

References 59 publications

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma

Oxidative DNA damage in disease—Insights gained from base excision repair glycosylase‐deficient mouse models

Effects of base excision repair proteins on mutagenesis by 8-oxo-7,8-dihydroguanine (8-hydroxyguanine) paired with cytosine and adenine

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