研究課題
特別研究員奨励費
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.
28年度が最終年度であるため、記入しない。
すべて 2017 2016 2015 2014 その他
すべて 雑誌論文 (8件) (うち査読あり 8件、 オープンアクセス 8件、 謝辞記載あり 8件) 学会発表 (8件) (うち国際学会 1件、 招待講演 7件) 図書 (2件) 備考 (1件)
Cell Cycle
巻: 14 ページ: 74-85
Genes to Cells
巻: 20 号: 3 ページ: 242-254
10.1111/gtc.12216
Mol. Cell
巻: 55 号: 1 ページ: 123-137
10.1016/j.molcel.2014.04.031
巻: 13 号: 12 ページ: 1859-1866
10.4161/cc.29251
Methods in Molecular Biology
巻: 1170 ページ: 279-293
10.1007/978-1-4939-0888-2_13
巻: 13 号: 6 ページ: 882-883
10.4161/cc.28216
Seminars in Cell & Developmental Biology,
巻: 30 ページ: 110-120
10.1016/j.semcdb.2014.04.014
PLoS Genetics
巻: 10 号: 10 ページ: 1-17
10.1371/journal.pgen.1004667
http://www.igakuken.or.jp/genome/