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Involvement of specialized DNA polymerases in mutagenesis by 8-hydroxy-dGTP in human cells
| 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) |
| URI: | http://hdl.handle.net/2115/38345 |
| 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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