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Roles of specialized DNA polymerases in mutagenesis by 8-hydroxyguanine in human cells
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) |
URI: | http://hdl.handle.net/2115/42891 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 紙谷 浩之
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