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タイトル: | In vivoevidence for translesion synthesis by the replicative DNA polymerase δ |
著者: | Hirota, Kouji Tsuda, Masataka Mohiuddin Tsurimoto, Toshiki Cohen, Isadora S. Livneh, Zvi Kobayashi, Kaori Narita, Takeo Nishihara, Kana Murai, Junko Iwai, Shigenori Guilbaud, Guillaume Sale, Julian E. Takeda, Shunichi |
著者名の別形: | 廣田, 耕志 津田, 雅貴 成田, 岳雄 西原, 佳那 村井, 純子 武田, 俊一 |
発行日: | 16-May-2016 |
出版者: | Oxford University Press (OUP) |
誌名: | Nucleic Acids Research |
巻: | 44 |
号: | 15 |
開始ページ: | 7242 |
終了ページ: | 7250 |
抄録: | The intolerance of DNA polymerase δ (Polδ) to incorrect base pairing contributes to its extremely high accuracy during replication, but is believed to inhibit translesion synthesis (TLS). However, chicken DT40 cells lacking the POLD3 subunit of Polδ are deficient in TLS. Previous genetic and biochemical analysis showed that POLD3 may promote lesion bypass by Polδ itself independently of the translesion polymerase Polζ of which POLD3 is also a subunit. To test this hypothesis, we have inactivated Polδ proofreading in pold3 cells. This significantly restored TLS in pold3 mutants, enhancing dA incorporation opposite abasic sites. Purified proofreading-deficient human Polδ holoenzyme performs TLS of abasic sites in vitro much more efficiently than the wild type enzyme, with over 90% of TLS events resulting in dA incorporation. Furthermore, proofreading deficiency enhances the capability of Polδ to continue DNA synthesis over UV lesions both in vivo and in vitro. These data support Polδ contributing to TLS in vivo and suggest that the mutagenesis resulting from loss of Polδ proofreading activity may in part be explained by enhanced lesion bypass. |
著作権等: | © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/226928 |
DOI(出版社版): | 10.1093/nar/gkw439 |
PubMed ID: | 27185888 |
出現コレクション: | 学術雑誌掲載論文等 |
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