Cloning and characterization of
 hOGG1
 , a human homolog of the
 OGG1
 gene of
 Saccharomyces cerevisiae

Radicella, J. Pablo; Dhérin, Claudine; Desmaze, Chantal; Ms, Fox; Boiteux, Serge

doi:10.1073/pnas.94.15.8010

Cited by 565 publications

(322 citation statements)

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“…The DNA glycosylases OGG1 and MUTYH excise 8-oxo-Gua bases paired with C, and A bases paired with 8-oxo-Gua, respectively [19][20][21][22][23][24][25][26][27][28][29]. Thus, both of these enzymes would be expected to suppress G:C → T:A transversions caused by the oxidation of G bases in DNA.…”

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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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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“…The presence of a similar system in mammals has been established by the recent cloning of the human and mouse OGG1 cDNAs (Lu et al, 1997;Arai et al, 1997; Abarutani et al, 1997;Rosenquist et al, 1997;Radicella et al, 1997;Roldan-Arjona et al, 1997;Bjoras et al, 1997). At least two messenger RNA forms have been identi®ed in human cells, coding for proteins of 345 and 424 amino acids with molecular weights of 39-kDa and 47-kDa, respectively (Lu et al, 1997;Arai et al, 1997; Abarutani et al, 1997;Rosenquist et al, 1997;Radicella et al, 1997;Roldan-Arjona et al, 1997;Bjoras et al, 1997). The biological signi®cance of this polymorphism has not yet been elucidated.…”

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confidence: 99%

“…A combination of cytogenetic and molecular studies have implicated loss of heterozygosity (LOH) or deletions in chromosome 3p in human lung and kidney cancers (Naylor et al, 1987;Yokota et al, 1987;Hibi et al, 1992). Some of these rearrangements could a ect the OGG1 gene which has been localised to 3p25-26 (Lu et al, 1997;Arai et al, 1997;Radicella et al, 1997;Roldan-Arjona et al, 1997;Bjoras et al, 1997). Furthermore, the analysis of the sequence changes in the p53 tumour suppressor gene showed that in lung and kidney cancers there is a bias in favour of GC to TA tranversions (Hollstein et al, 1996).…”

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confidence: 99%

“…However, the 39-kDa form of hOgg1 protein, refered as the a-form, seems to be the most abundant and is localized in the nucleus (Bjoras et al, 1997;Boiteux and Radicella, 1998). The a-hOgg1 protein is an 8-OxoG DNA glycosylase/AP lyase that complements the mutator phenotype of the ogg1 mutants of S. cerevisiae (Radicella et al, 1997). By analogy with the yeast system, inactivation of the OGG1 gene in human cells could lead to a mutator phenotype due to unrepaired 8-OxoG in DNA.…”

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Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours

et al. 1998

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The human OGG1 gene encodes a DNA glycosylase activity catalysing the excision of the mutagenic lesion 7,8-dihydro-8-oxoguanine from oxidatively damaged DNA. The OGG1 gene was localized to chromosome 3p25, a region showing frequent loss of heterozygosity (LOH) in lung and kidney tumours. In this study, we have analysed by RT ± PCR the expression of OGG1 in 25 small cell lung cancers, in 15 kidney carcinomas and the 15 normal kidney counterparts. The results show that OGG1 messenger RNA can be detected in all tumours tested and that no signi®cant di erence was observed in the level of expression between normal and tumoral kidney tissues. Denaturing gradient gel electrophoresis (DGGE) was used to screen this series of human tumours for alterations in the OGG1 cDNA. The study revealed homozygous mutations in three tumours, two from lung and one from kidney. Sequencing analysis of the mutants identi®ed a single base substitution in each of the three cases: two tranversions (GC to TA and TA to AT) and one transition (GC to AT). All three substitutions cause an amino acid change in the hOgg1 protein. For the mutant kidney tumour, the normal tissue counterpart shows a wild-type pro®le. These results suggest a role for OGG1 mutations in the course of the multistage process of carcinogenesis in lung or kidney.Keywords: oxidative DNA damage; DNA repair; missense mutations of OGG1 gene; human lung and kidney cancer; tumour suppressor gene Damage to DNA by oxygen-free radicals is postulated to cause mutations that are associated with the initiation or the progression of human cancers (Breimer, 1990;Loeb, 1997;Beckman and Ames, 1997). Oxidative damage-induced mutations can activate oncogenes or inactivate tumour suppressor genes altering the cell growth control (Fearon, 1997). An oxidatively damaged guanine, 7,, is abundantly produced in DNA as a consequence of the cellular oxidative metabolism or the exposure to ionizing radiation or chemical carcinogens (Dizdaroglu, 1991;Cadet et al., 1997). The presence of 8-OxoG in DNA has been shown to be mutagenic since, while this lesion does not impede DNA chain elongation, it preferentially pairs with adenine during in vitro DNA synthesis (Shibutani et al., 1991). The biological incidence of the presence of 8-OxoG in DNA has been unveiled by the study of two genes in E. coli, fpg (mutM) and mutY (micA) which code for DNA glycosylases that cooperate to prevent the mutagenic e ects of 8-OxoG in DNA (Boiteux et al., 1987;Cabrera et al., 1988;Radicella et al., 1988;Nghiem et al., 1988;Au et al., 1989). Inactivation of either gene leads to a spontaneous mutator phenotype characterized by the exclusive increase in GC to TA transversions (Michaels and Miller, 1992;Grollman and Moriya, 1993;Boiteux and Laval, 1997). In Saccharomyces cerevisiae the OGG1 gene was cloned as the functional eukaryotic homologue of the bacterial fpg gene (Au ret van der Kemp et al., 1996). The yeast Ogg1 protein is a DNA glycosylase/AP lyase which excises 8-OxoG, formamidopyrimidines and incizes apurinic/apyrimid...

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“…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.…”

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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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Cloning and characterization of hOGG1 , a human homolog of the OGG1 gene of Saccharomyces cerevisiae

Cited by 565 publications

References 43 publications

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

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

Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours

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

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