Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites

by 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 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 a ffects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Usingin 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...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research