オバラ　チズカ   Obara Chizuka   小原　千寿香    所属   東邦大学  理学部 生物学科    職種   博士研究員
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites.
掲載誌名	正式名：PLoS genetics ISSNコード：1553-7390
掲載区分	国外
巻・号・頁	14(3),pp.e1007277
著者・共著者	Takeshi Yasuda,Wataru Kagawa,Tomoo Ogi,Takamitsu A Kato,Takehiro Suzuki,Naoshi Dohmae,Kazuya Takizawa,Yuka Nakazawa,Matthew D Genet,Mika Saotome,Michio Hama,Teruaki Konishi,Nakako Izumi Nakajima,Masaharu Hazawa,Masanori Tomita,Manabu Koike,Katsuko Noshiro,Kenichi Tomiyama,Chizuka Obara,Takaya Gotoh,Ayako Ui,Akira Fujimori,Fumiaki Nakayama,Fumio Hanaoka,Kaoru Sugasawa,Ryuichi Okayasu,Penny A Jeggo,Katsushi Tajima
発行年月	2018/03
概要	The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis. An immunofluorescence microscopy analysis revealed that RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism.
DOI	10.1371/journal.pgen.1007277
PMID	29590107