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

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Title: Roles of specialized DNA polymerases in mutagenesis by 8-hydroxyguanine in human cells
Authors: Kamiya, Hiroyuki Browse this author
Yamaguchi, Ayaka Browse this author
Suzuki, Tetsuya Browse this author
Harashima, Hideyoshi Browse this author
Keywords: 8-Hydroxyguanine
specialized DNA polymerases
oxidative mutagenesis
Issue Date: 1-Apr-2010
Publisher: Elsevier B.V.
Journal Title: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
Volume: 686
Issue: 1-2
Start Page: 90
End Page: 95
Publisher DOI: 10.1016/j.mrfmmm.2010.02.001
PMID: 20153758
Abstract: The formation of 8-hydroxyguanine (8-OH-Gua, 7,8-dihydro-8-oxoguanine) in DNA and in the nucleotide pool results in G:C→T:A and A:T→C:G substitution mutations, respectively, due to the ability of 8-OH-Gua to pair with both C and A. In this study, shuttle plasmid DNAs containing 8-OH-Gua paired with C and A in the supF gene were transfected into human 293T cells, in which specialized DNA polymerases were knocked-down. The DNAs replicated in the cells were recovered and then introduced into an indicator strain of Escherichia coli. Mutation analysis indicated that the knock-downs of DNA polymerases η and ζ by siRNAs enhanced the G:C→T:A mutations caused by 8-OH-Gua:C. The 8-OH-Gua:C-induced mutation frequency was not further increased by double knock-downs of DNA polymerases η and ζ, suggesting that the two DNA polymerases work in the same pathway. In addition, the reduction of DNA polymerase η slightly decreased the A:T→C:G substitutions caused by 8-OH-Gua:A. These results suggest that DNA polymerases η and ζ are involved in the bypass of 8-OH-Gua in human cells.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 紙谷 浩之

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