| 研究分担者 |
富山 健一 国立研究開発法人国立精神・神経医療研究センター, その他部局等, 研究員(移行) (20584064)
滝澤 和也 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, 研究員(任非) (20739388)
安田 武嗣 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)
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, 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(任非) (90415977)
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| 研究実績の概要 |
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, was defective in sustained colocalization at DSB sites, and HR was not performed. A reporter assay for HR, comprising two inactive GFP genes in a direct repeat orientation, showed that either SIRT2 or SIRT3 depletion inhibits HR repair in the same manner as RAD52 depletion. These findings suggest that HR requires the regulation of RAD52 acetylation and deacetylation. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism.
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