Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells

Satou, Kazuya; Kawai, Kazuaki; Kasai, Hiroshi; Harashima, Hideyoshi; Kamiya, Hiroyuki

doi:10.1016/j.freeradbiomed.2007.02.024

Cited by 40 publications

(35 citation statements)

References 57 publications

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“…Previously, we reported that A:T → C:G transversions were specifically induced by 8-oxo-dGTP in mammalian cells [48,51]. In this study, we examined the mutagenic potential of 8-oxo-dGTP in cells with knocked-down DNA glycosylases.…”

Section: Decrease In 8-oxo-dgtp-induced Mutations By Knock-down Of Mutyhmentioning

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: Decrease In 8-oxo-dgtp-induced Mutations By Knock-down Of Mutyhmentioning

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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“…Pursell et al demonstrated that the concentration of 8-OH-dGTP was 1-10% of that of unmodified dGTP in the mitochondrial nucleotide pool [18]. 8-OH-dGTP is mutagenic and specifically induced A:TC:G transversions in living bacterial and mammalian cells [19][20][21]. The A:TC:G mutations seem to be triggered by the incorporation of 8-OH-dGTP opposite A in template DNA, resulting in the formation of 8-OH-Gua:A base pairs, and the subsequent incorporation of dCTP opposite 8-OH-Gua during the next round of replication would cause the transversion [22].…”

Section: -Oh-gua Is Highly Mutagenic and Induces G:ct:a Transversiomentioning

confidence: 99%

“…8-OH-Gua was introduced into positions 122 and 96 of the sense strand of the supF gene for 8-OH-Gua:C and 8-OH-Gua:A, respectively. Position 96 was one of the 9 A:TC:G hot spots in the supF gene when 8-OH-dGTP was introduced [20,21]. Plasmid DNAs containing G:C and T:A at positions 122 and 96, respectively, were used as control plasmids.…”

Section: Design Of Plasmid Dnas Involving 8-oh-guamentioning

confidence: 99%

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Roles of specialized DNA polymerases in mutagenesis by 8-hydroxyguanine in human cells

Kamiya

Yamaguchi

Suzuki

et al. 2010

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…The mutagenicity of 8-OH-dGTP in mammalian cells was examined by the introduction of 8-OH-dGTP plus shuttle plasmid DNA containing the supF gene into simian COS-7 and human 293T cells [18,19]. The oxidized form of dGTP induced A:TC:G substitution mutations in mammalian cells, as in E. coli cells.…”

Section: Induced Mutations In Mammalian Cellsmentioning

confidence: 99%

Mutagenicity of oxidized DNA precursors in living cells: Roles of nucleotide pool sanitization and DNA repair enzymes, and translesion synthesis DNA polymerases

Kamiya

2010

Mutation Research/Genetic Toxicology and Environmental Mutagene

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The base moieties of DNA precursors in the nucleotide pool are subjected to oxidative damage, and the formation of damaged DNA precursors is an important source of mutagenesis. 8-Hydroxy-2'-deoxyguanosine 5'-triphosphate, also known by the name of its keto-enol tautomer as 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate, and 2-hydroxy-2'-deoxyadenosine 5'-triphosphate have been identified as the major products of in vitro oxidation reactions. The mutagenicities of these damaged precursors in living cells will be summarized in this review. In addition, the roles of the nucleotide pool sanitization and DNA repair enzymes, and the translesion synthesis DNA polymerases will be described.

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Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells

Cited by 40 publications

References 57 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

Roles of specialized DNA polymerases in mutagenesis by 8-hydroxyguanine in human cells

Mutagenicity of oxidized DNA precursors in living cells: Roles of nucleotide pool sanitization and DNA repair enzymes, and translesion synthesis DNA polymerases

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