ニシ リョウタロウ
西 良太郎 所属 応用生物学部 応用生物学科 職種 准教授 |
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言語種別 | 英語 |
発行・発表の年月 | 2017/01 |
形態種別 | 学術論文 |
査読 | 査読あり |
標題 | BRCA1 directs the repair pathway to homologous recombination by promoting 53BP1 dephosphorylation |
執筆形態 | 共著 |
掲載誌名 | Cell Reports |
掲載区分 | 国外 |
出版社・発行元 | CELL PRESS |
巻・号・頁 | 18,pp.520-532 |
総ページ数 | 14 |
国際共著 | 国際共著 |
著者・共著者 | Mayu Isono, Atsuko Niimi, Takahiro Oike, Yoshihiko Hagiwara, Hiro Sato, Ryota Sekine, Yukari Yoshida, Shin-Ya Isobe, Chikashi Obuse, Ryotaro Nishi, Elena Petricci, Shinichiro Nakada, Takashi Nakano and Atsushi Shibata |
概要 | BRCA1 promotes homologous recombination (HR) by activating DNA-end resection. By contrast, 53BP1 forms a barrier that inhibits DNA-end resection. Here, we show that BRCA1 promotes DNA-end resec-tion by relieving the 53BP1-dependent barrier. We show that 53BP1 is phosphorylated by ATM in S/G2 phase, promoting RIF1 recruitment, which inhibits resection. 53BP1 is promptly dephosphorylated and RIF1 released, despite remaining unrepaired DNA double-strand breaks (DSBs). When resection is impaired by CtIP/MRE11 endonuclease inhibition, 53BP1 phosphorylation and RIF1 are sustained due to ongoing ATM signaling. BRCA1 depletion also sus-tains 53BP1 phosphorylation and RIF1 recruitment. We identify the phosphatase PP4C as having a major role in 53BP1 dephosphorylation and RIF1 release. BRCA1 or PP4C depletion impairs 53BP1 reposition-ing, EXO1 recruitment, and HR progression. 53BP1 or RIF1 depletion restores resection, RAD51 loading, and HR in PP4C-depleted cells. Our findings suggest that BRCA1 promotes PP4C-dependent 53BP1 dephosphorylation and RIF1 release, directing repair toward HR. |
DOI | https://doi.org/10.1016/j.celrep.2016.12.042 |
論文(査読付)ファイル | DOWNLOAD |