Mutagenic Bypass of 8-Oxo-7,8-dihydroguanine (8-Hydroxyguanine) by DNA Polymerase κ in Human Cells
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- Hiroyuki Kamiya
- Graduate School of Science and Engineering, Ehime University, 2-5 Bunkyo-cho, Matsuyama 790-8577, Japan
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- Masahiro Kurokawa
- Graduate School of Science and Engineering, Ehime University, 2-5 Bunkyo-cho, Matsuyama 790-8577, Japan
書誌事項
- 公開日
- 2012-07-30
- DOI
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- 10.1021/tx300259x
- 公開者
- American Chemical Society (ACS)
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説明
The formation of 8-oxo-7,8-dihydroguanine (G(O), 8-hydroxyguanine) in DNA and in the nucleotide pool results in G:C→T:A and A:T→C:G substitution mutations, respectively, since G(O) can pair with both C and A. In this study, the role of DNA polymerase κ in the mutagenicity of G(O) was investigated, using a supF shuttle plasmid propagated in human U2OS cells. This translesion synthesis DNA polymerase was knocked down by siRNA, and plasmid DNAs containing G(O):C and G(O):A pairs were transfected into the knock-down cells. The supF plasmid DNAs replicated in the cells were then introduced into Escherichia coli. Mutation analyses indicated that the knock-down of DNA polymerase κ by siRNA decreased the frequency of G:C→T:A mutation caused by G(O):C, although no effects of the DNA polymerase κ reduction were observed for the A:T→C:G substitution induced by G(O):A. These results suggested that DNA polymerase κ is involved in the mutagenic bypass of G(O) in living human cells, when the damaged base is generated by direct DNA oxidation.
収録刊行物
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- Chemical Research in Toxicology
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Chemical Research in Toxicology 25 (8), 1771-1776, 2012-07-30
American Chemical Society (ACS)
