Involvement of specialized DNA polymerases in mutagenesis by 8-hydroxy-dGTP in human cells
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概要
- 論文の詳細を見る
The mutagenicity of an oxidized form of dGTP, 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (8-OH-dGTP), was examined using human 293T cells. Shuttle plasmid DNA containing the supF gene was first transfected into the cells, and then 8-OH-dGTP was introduced by means of osmotic pressure. The DNAs replicated in the cells were recovered and then transfected into Escherichia coli. 8-OH-dGTP induced A:T → C:G substitution mutations in the cells. The knock-downs of DNA polymerases η and ζ, and REV1 by siRNAs reduced the A:T → C:G substitution mutations, suggesting that these DNA polymerases are involved in the misincorporation of 8-OH-dGTP opposite A in human cells. In contrast, the knock-down of DNA polymerase ι did not affect the 8-OH-dGTP-induced mutations. The decrease in the induced mutation frequency was more evident by double knock-downs of DNA pols η plus ζ and REV1 plus DNA pol ζ (but not by that of DNA pol η plus REV1), suggesting that REV1-DNA pol η and DNA pol ζ work in different steps. These results indicate that specialized DNA polymerases are involved in the mutagenesis induced by the oxidized dGTP.
- Elsevierの論文
- 2009-05-01
著者
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原島 秀吉
北大院・薬学研究科
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Hori Mika
北海道大学 薬学研究科
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Hori Mika
北海道大学 薬学研究院
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Hori Mika
Hokkaido University Graduate School Of Pharmaceutical Sciences
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Kamiya Hiroyuki
産業医科大学産業生態科学研究所
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Murata-kamiya Naoko
Inst. Indust. Ecolog. Sci. Univ. Occup. Environ. Hith.
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Kaji Hiroshi
Inst. Indust. Ecolog. Sci. Univ. Occup. Environ. Hith.
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