<i>Mmh</i>
            /
            <i>Ogg1</i>
            gene inactivation results in accumulation of 8-hydroxyguanine in mice

Minowa, Osamu; Arai, T.; Hirano, Masanori; Monden, Yoshiaki; Nakai, Shigeyasu; Fukuda, Mayuko; Itoh, Masaki; Takano, Hiroshi; Hippou, Yoshitaka; Aburatani, Hiroyuki; Masumura, Ken-ichi; Nohmi, Takehiko; Nishimura, Susumu; Noda, Tetsuo

doi:10.1073/pnas.050404497

Cited by 331 publications

(233 citation statements)

References 23 publications

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“…Similarly, a novel model of OGG1 deficiency also reported a significant increase in 8-oxoG lesions, associated with increased mutagenesis of a transgenic gpt gene [Minowa et al, 2000;Arai et al, 2002Arai et al, , 2003]. However, no increase in spontaneous tumors was detected in this strain of Ogg1 2/2 mice.…”

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

confidence: 88%

“…The primary substrates recognized by OGG1 include 8-oxoguanine (8-oxoG), the most commonly formed oxidative DNA lesion, and the formamidopyrimidine derivative of guanine (FapyG). Extracts from mice lacking OGG1 have consistently demonstrated increased accumulation of these lesions [Minowa et al, 2000;Nishimura, 2001;Hu et al, 2005]. However, as discussed below, the relationship between the increased number of lesions and pathological states is not always straightforward.…”

Section: Ogg1mentioning

confidence: 99%

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

confidence: 88%

Section: Ogg1mentioning

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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“…The four DNA glycosylases each function in the suppression of mutations by 8-oxo-Gua in DNA. The overlapped recognition of 8-oxo-Gua could explain the fact that single knock-out mice deficient in OGG1, MUTYH, NTH1, and NEIL1 show few tumor phenotypes [57,[65][66][67][68][69][70][71]. In contrast, there is evidence to support the view that polymorphisms in these DNA glycosylases are associated with human carcinogenesis (reviewed in 72).…”

Section: Discussionmentioning

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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“…1 Also, these knockout mice do not have an increased rate of developing malignancy. 1,17 Additionally, although the number of cases is relatively small in this study, hOGG1 expression in follicular lymphoma did not correlate with disease stage at presentation, overall survival, or response to therapy (data not shown). Taken together, our findings suggest that downregulation of hOGG1 expression may be an early event in lymphomagenesis.…”

Section: Discussionmentioning

confidence: 61%

Expression of human 8-oxoguanine DNA glycosylase (hOGG1) in follicular lymphoma

et al. 2005

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The human homologue of the yeast DNA repair enzyme 8-oxoguanine DNA glycosylase (hOGG1) repairs oxidatively damaged guanosine nucleotides in DNA. This enzyme is highly expressed in reactive germinal centers, where lymphoid cells are under oxidative stress, and has been thought to protect lymphocytes from mutation. As a first step to investigate the role of hOGG1 in lymphomagenesis, we evaluated hOGG1 expression in follicular lymphoma. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue of 28 follicular lymphoma cases (16 grade 1, seven grade 2, and five grade 3) to evaluate the expression of hOGG1 in neoplastic follicles. Reactive germinal centers of non-neoplastic tonsil and lymph node tissue were also examined. Fluorescent-in-situ hybridization (FISH) was performed using a DNA probe from BAC clone RP11-266J6 corresponding to 3p25, where the hOGG1 gene resides, to evaluate for the presence or absence of a deletion. In reactive germinal centers, the majority of centroblasts and centrocytes were positive for hOGG1. In contrast, the majority (21 of 28 or 75%) of follicular lymphoma cases showed absent/minimal expression of hOGG1. Only four of 28 (14%) follicular lymphoma cases revealed the same levels of hOGG1 expression as reactive germinal centers. There was no correlation between hOGG1 expression and histologic grade. None of the 16 cases evaluated by FISH showed a deletion of hOGG1. Furthermore, absent/minimal hOGG1 expression was observed in four of six Bcl-2-negative follicular lymphoma cases. Our findings suggest that absent/minimal hOGG1 expression occurs in the majority of follicular lymphomas. The downregulation of hOGG1 does not appear to be due to a deletion of the hOGG1 locus. Additionally, finding absent/minimal hOGG1 expression in a subset of Bcl-2-negative follicular lymphomas suggests that hOGG1 may have utility in diagnosing Bcl-2-negative follicular lymphomas. Keywords: follicular lymphoma; hOGG1; immunohistochemistry The human homologue of the yeast DNA repair enzyme, 8-oxoguanine-DNA glycosylase (hOGG1), excises 8-oxoguanine, an oxidative form of the guanine nucleotide. 1 HOGG1 shares a 38% identity with the yeast OGG1. It has been localized to chromosome 3p25 by fluorescent-in-situ hybridization (FISH) by Radicella et al in 1997, 2 and it was cloned by Rosenquist et al 3 in 1997. This DNA glycosylase/apurinic lyase repairs oxidative DNA damage, specifically 8-oxoguanine/C base pairs. 8-hydroxyguanine is highly mutagenic via GC to TA transversions 4 and is generated by oxidative stresses as well as normal cellular metabolism. 5 It is believed that hOGG1's role of excising 8-oxoguanine protects DNA against the mutagenic effects of oxidative damage and decreased cell survival from radiation-induced damage. 6 Supporting hOGG1's role of hindering mutagenesis is that certain a genetic polymorphism of hOGG1, Ser326Cys, has been implicated in an increased incidence of adenocarcinoma of the lung 7 and squamous cell carcinoma of the lung 8,9 in patients with the Cys/Cys genoty...

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Mmh / Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice

Cited by 331 publications

References 23 publications

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

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

Expression of human 8-oxoguanine DNA glycosylase (hOGG1) in follicular lymphoma

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