| Project/Area Number |
18K07248
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | DNA修復 / DSB応答タンパク質 / ユビキチン化 / 脱ユビキチン化 |
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| Outline of Final Research Achievements |
BRCA1 and BARD1, proteins involved in tumor suppression, form a dimer. BAP1, which was thought to inhibit this dimer formation, was found to bind to BRCA1 in the presence of CK2α/CK2β and form a protein complex of BRCA1/BARD1/BAP1/CK2.
BAP1 and CK2 bind at the time of DNA damage and perform post-translational modifications including phosphorylation of BAP1. This suggests that the newly discovered complex is involved in DNA repair that occurs as a subsequent event after DNA damage.
This research project has elucidated a new signaling pathway for DNA damage response and DNA repair through the interaction of BRCA1, which functions as a tumor suppressor, with the newly discovered protein.
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| Academic Significance and Societal Importance of the Research Achievements |
DNA損傷応答時やDNA修復が機能不全を起こすと癌化が起きる。今回の新たな複合体の発見はBRCA1の癌抑制に関わる新たなメカニズムが解明できると考える。 また、DNA損傷時の役割を解明すればDNAを傷つけるタイプの癌化学療法や放射線療法における効果の改善に役立ち抗癌剤の適応の指標となると考える。
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