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
| Project/Area Number |
14F03511
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 外国 |
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| Research Field |
Architectural history/Design
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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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)
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| 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
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
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| Project Period (FY) |
2014-04-25 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2015: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Rif1 / yKu70 / Double-strand DNA break / DNA replication / Replication origin / Late and dormant origin / Telomere / Budding yeast / Double-strand break / Dormant origins |
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| 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.
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| Research Progress Status |
28年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
28年度が最終年度であるため、記入しない。
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Report
(2 results)
Research Products
(19 results)
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[Journal Article] CDC28 phosphorylates Cac1p and regulates the association of Chromatin Assembly Factor I with chromatin.2015
Author(s)
Jeffery, D., Kakusho, N., You, Z., Gharib, M., Wyse, B., Drury, E., Weinreich, M., Thibault, P. Verreault, A., Masai, H. and Yankulov, K.
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Journal Title
Cell Cycle
Volume: 14
Pages: 74-85
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] NCOA4 Transcriptional Coactivator Inhibits Activation of DNA Replication Origins.2014
Author(s)
Bellelli, R., Castellone, M.D., Guida, T., Limongello, R., Dathan, N.A., Merolla, F., Cirafici, A.M., Affuso, A., Masai, H., Costanzo, V., Grieco, D., Fusco, A., Santoro, M., and Carlomagno, F.
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Journal Title
Mol. Cell
Volume: 55
Issue: 1
Pages: 123-137
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] H2B Mono-ubiquitylation Facilitates Fork Stalling and Recovery during Replication Stress by Coordinating Rad53 Activation and Chromatin Assembly2014
Author(s)
Chia-Yeh Lin, Meng-Ying Wu, Sophie Gay, Lisette Marjavaara, Mong Sing Lai, Wei-Chun Hsiao, Shih-Hsun Hung, Hsin-Yi Tseng, Duncan Edward Wright, Chen-Yi Wang, Guoo-Shyng W. Hsu, Didier Devys, Andrei Chabes, and Cheng-Fu Kao
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Journal Title
PLoS Genetics
Volume: 10
Issue: 10
Pages: 1-17
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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