2016 Fiscal Year Annual Research Report

二本鎖ＤＮＡ切断により誘導される複製プログラム変動のメカニズム

Research Project

Project/Area Number	14F03511
Research Institution	Tokyo Metropolitan Institute of Medical Science
Principal Investigator	正井久雄公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 副所長 (40229349)
Co-Investigator(Kenkyū-buntansha)	LAI MONG SING 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 外国人特別研究員
Project Period (FY)	2014-04-25 – 2017-03-31
Keywords	Rif1 / yKu70 / Double-strand DNA break / DNA replication / Replication origin / Late and dormant origin / Telomere / Budding yeast
Outline of Annual Research Achievements	Various types of DNA damage can induce activation of dormant replication origins. Previous studies showed that a single and irrepairable double-strand break (DSB) in the proximity of a dormant replication origin is able to promote origin firing, likely to rescue replication of the broken chromosome fragment (Doksani et al., Cell 2009). In this study, We aim at elucidating the mechanisms leading to dormant origin firing following DSB formation. Here we showed that DNA damage checkpoints do not counteract DSB-induced dormant origin firing but the dormant origin firing activities are counteracted by histone acetylation state. We also identified telomere-related proteins, Rif1 and Ku complex, as potential regulators of dormant origins even in the absence of DSB. We found that Rif1 and yKu70 bind preferentially at regions between dormant origins and DSB site but not at the other side of the DSB site. The binding profiles of Rif1 and yKu70 at those regions are not affected by DSB formation. Besides, we found that absence of yKu70 prevents Rif1 from binding at regions between dormant origins and DSB site. Our results indicate an important role of Rif1 and yKu70 in controlling dormant origin activity near to DSB site.
Research Progress Status	28年度が最終年度であるため、記入しない。
Strategy for Future Research Activity	28年度が最終年度であるため、記入しない。