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
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
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