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Involvement of specialized DNA polymerases in mutagenesis by 8-hydroxy-dGTP in human cells

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Title: Involvement of specialized DNA polymerases in mutagenesis by 8-hydroxy-dGTP in human cells
Authors: Satou, Kazuya Browse this author
Hori, Mika Browse this author
Kawai, Kazuaki Browse this author
Kasai, Hiroshi Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Kamiya, Hiroyuki Browse this author
Keywords: 8-Hydroxy-dGTP
specialized DNA polymerases
oxidative mutagenesis
nucleotide pool
Issue Date: 1-May-2009
Publisher: Elsevier
Journal Title: DNA Repair
Volume: 8
Issue: 5
Start Page: 637
End Page: 642
Publisher DOI: 10.1016/j.dnarep.2008.12.009
PMID: 19179121
Abstract: 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.
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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