| Project/Area Number |
26740016
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Tokyo University of Technology (2016)
St. Marianna University School of Medicine (2014-2015) |
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Principal Investigator |
UI Ayako 東京工科大学, 応用生物学部, 准教授 (00469967)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | DNA修復 / 転写 / ポリコーム / ENL / ATM / がん / MLLT1 / Polycomb / ゲノム安定性 / DSB / PRC1 / ユビキチン |
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| Outline of Final Research Achievements |
ENL (MLLT1), a factor of Super Elongation Complex (SEC) and fusion partner of the Mixed-Lineage-Leukemia (MLL) protein, activates transcription. Here we found that ENL interacts with BMI1/RING1B, the E3-ubiquitin-ligase of PRC1 (Polycomb Repressive Complex 1). After DSB, ENL is phosphorylated by ATM at its well-conserved SQ-sites and increase its interaction with BMI1. Then, ENL recruits Polycomb at transcription sites near DSBs to repress transcription by promoting ubiquitination of H2A. Furthermore, the function of ENL is required for the recruitment of DSB repair proteins at DSB sites near transcription sites and DSB repair. These results suggest that under the control of ATM, ENL recruits PRC1 at transcriptional elongation sites to repress transcription and promotes DSB repair. This mechanism ensures a rapid and systematic transcriptional repression by DSBs to secure cellular homeostasis and genome integrity.
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