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Mutagenic bypass of 8-oxo-7,8-dihydroguanine (8-hydroxyguanine) by DNA polymerase κ in human cells.

Abstract：

: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.

journal_name

Chem Res Toxicol

journal_title

Chemical research in toxicology

authors

Kamiya H,Kurokawa M

doi

10.1021/tx300259x

subject

Has Abstract

pub_date

2012-08-20 00:00:00

pages

1771-6

issue

8

eissn

0893-228X

issn

1520-5010

journal_volume

25

pub_type

杂志文章

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