Mechanism of genomic DNA damage response mediated by acetylation of non-histone proteins

2017 Fiscal Year Final Research Report

• Project/Area Number: 26281026
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: YASUDA Takeshi 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, 主任研究員(定常) (60332269)
• Co-Investigator(Kenkyū-buntansha): 増本 博司 長崎大学, 医歯薬学総合研究科(医学系), 講師 (80423151) ; 荻 朋男 名古屋大学, 環境医学研究所, 教授 (80508317) ; 小原 千寿香 (逸見千寿香) 国立研究開発法人量子科学技術研究開発機構, 緊急被ばく医療研究センター, 研究員 (90415977)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: DNA損傷応答 / アセチル化 / 脱アセチル化 / DNA相同組換え / RAD52 / p300 / CBP / RAD51

Outline of Final Research Achievements

We newly identified several non-histone proteins involved in DNA damage response, which are acetylated by p300 and CBP histone acetyltransferases in vitro. Among the identified acetylated proteins, we showed that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DNA double strand break (DSB) sites. We identified 13 acetylation sites in RAD52. We revealed 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, we demonstrated that the acetylation of RAD52 is linked to ATM signaling. Our findings clarify the importance of RAD52 acetylation in HR.

Free Research Field

分子生物学