Recognition of the oxidized lesions spiroiminodihydantoin and guanidinohydantoin in DNA by the mammalian base excision repair glycosylases NEIL1 and NEIL2

Hailer, M. Katie; Slade, Peter G.; Martin, Brooke D.; Rosenquist, Thomas A.; Sugden, Kent D.

doi:10.1016/j.dnarep.2004.07.006

Cited by 153 publications

(175 citation statements)

References 31 publications

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“…We have recently analyzed the HPRT mutational spectra in NEIL2-deficient cells, where the majority of mutations were generated at C•G base pairs (data not shown). This is consistent with the substrate preference of NEIL2 for mutagenic oxidation products of C and G (including 8-oxoguanine) [14,41]. We and others have shown that NEIL1 has broad substrate specificity in that it preferentially excises formamidopyrymidine (Fapy)-adenine (FapyA), Fapyguanine (Fapy G), thymine glycol, 5-hydroxyuracil (5-OHU) and several other pyrimidine derivatives [13,15,16] in vitro.…”

Section: Discussionsupporting

confidence: 82%

Mutator phenotype of mammalian cells due to deficiency of NEIL1 DNA glycosylase, an oxidized base-specific repair enzyme

et al. 2008

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The recently characterized NEIL1 and NEIL2 are distinct from the previously characterized mammalian DNA glycosylases (OGG1 and NTH1) involved in repair of oxidized bases because of the NEILs' preference for excising base lesions from single-stranded DNA present in bubble and fork structures. OGG1 and NTH1 are active only with duplex DNA. This raises the possibility that NEILs function in the repair of base lesions during DNA replication and/or transcription. S-phasespecific activation of only NEIL1 suggests its preferential involvement in repair during DNA replication. Here we show that antisense oligonucleotides specific for human or Chinese hamster NEIL1 decreased in vivo NEIL1 levels by 70-80%, concomitant with increased oxidative damage in the genome. Moreover, NEIL1 downregulation enhanced spontaneous mutation in the HPRT locus by about 3-fold in both Chinese hamster V79 and human bronchial A549 cell lines. The mutant frequency was further enhanced (7-to 8-fold) under oxidative stress. The majority of both spontaneous and induced mutations occurred at A•T base pairs, indicating that oxidized A and/or T are NEIL1's preferred in vivo substrates. NEIL1 thus plays a distinct and important role in repairing endogenous and induced mutagenic oxidized bases, and hence in maintaining the functional integrity of mammalian genomes.

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Section: Discussionsupporting

confidence: 82%

Mutator phenotype of mammalian cells due to deficiency of NEIL1 DNA glycosylase, an oxidized base-specific repair enzyme

et al. 2008

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“…Our recent data show that Sp and Gh are two major oxidation products formed after treating telomeric G-quadruplex DNA with several oxidant systems in vitro (54). Moreover, Sp and Gh are the two best substrates for mNeil3 (13) and NEIL1 (40); NEIL2 (55) and Nth (56) also excise the two hydantoin lesions. We thus tested the activity of the glycosylases on Sp-containing and Ghcontaining quadruplex substrates (qTel-Sp and qTel-Gh).…”

Section: Journal Of Biological Chemistry 27265mentioning

confidence: 95%

Neil3 and NEIL1 DNA Glycosylases Remove Oxidative Damages from Quadruplex DNA and Exhibit Preferences for Lesions in the Telomeric Sequence Context

Zhou

Liu

Fleming

et al. 2013

Journal of Biological Chemistry

109

134

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“…Like OGG1, NTH1 belongs to the E. coli NTH family of glycosylases that contain a conserved helix-hairpin-helix motif while the NEIL glycosylases, of which there are three known isoforms NEIL1, NEIL2, and NEIL3, belong to the MUTM/NEI family of glycosylases [Hazra et al, 2002a, b;Dou et al, 2003;Rosenquist et al, 2003]. NEIL1 acts on wide-ranging substrates, including thymine glycols (Tg), 5-hydroxyuracil, further oxidized products of 8-oxoG including guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp), and oxidatively damaged purine lesions including the foramidopyrimidine derivative of adenine (FapyA) or FapyG [Hazra et al, 2002a, b;Dou et al, 2003;Rosenquist et al, 2003;Hailer et al, 2005]. NTH1 is thought to have largely overlapping substrate specificity with NEIL1 except that NTH1 is not able to act on FapyAs or certain steroisomers of Tg [Aspinwall et al, 1997;Dizdaroglu et al, 1999;Rosenquist et al, 2003].…”

Section: Neil1^3 and Nth1mentioning

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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Recognition of the oxidized lesions spiroiminodihydantoin and guanidinohydantoin in DNA by the mammalian base excision repair glycosylases NEIL1 and NEIL2

Cited by 153 publications

References 31 publications

Mutator phenotype of mammalian cells due to deficiency of NEIL1 DNA glycosylase, an oxidized base-specific repair enzyme

Mutator phenotype of mammalian cells due to deficiency of NEIL1 DNA glycosylase, an oxidized base-specific repair enzyme

Neil3 and NEIL1 DNA Glycosylases Remove Oxidative Damages from Quadruplex DNA and Exhibit Preferences for Lesions in the Telomeric Sequence Context

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

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