Elucidation of homologous recombination repair by mRNA processing and application to ovarian cancer treatment
| Project/Area Number |
18K16759
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 卵巣癌 / DNA損傷修復 / 相同組換え修復 / mRNAプロセッシング / スプライシング / 相同組換修復 / BRCA1 / メディエーター複合体 |
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| Outline of Final Research Achievements |
In this research project, we revealed the role of the mediator complex as a novel DNA damage repair factor in maintaining genomic stability. Specifically, in comprehensive genome wide screens, we extracted mediator complex factors as novel DNA damage candidate factors and identified which steps in the DNA damage repair pathway are regulated. In addition, we established an experimental system for observing the dynamics of a novel factor at the DNA damage site using live cell imaging technique by a confocal microscope, and identified the upstream regulatory pathway by inhibitors and siRNA. The mRNA processing pathway involving the mediator complex is frequently mutated in multiple cancer types, suggesting that it may become a novel therapeutic marker or target in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
新規のDNA損傷修復因子としてmRNAプロセッシングに関わるメディエーター複合体を同定した。DNA損傷修復、特に相同組換え修復能の異常は卵巣癌の治療標的として確立されており、メディエーター複合体の機能失活が相同組換え修復異常につながる可能性を初めて示すことになる。メディエーター複合体を含むmRNAプロセッシング経路は複数の癌種で高頻度に変異を呈しており、将来的には新規の治療マーカーや治療標的につなげられる可能性がある。
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] Interleukin-17 is associated with expression of programmed cell death 1 ligand 1 in ovarian carcinoma.2019
Author(s)
Aotsuka A, Matsumoto Y, Arimoto T, Kawata A, Ogishima J, Taguchi A, Tanikawa M, Sone K, Mori-Uchino M, Tsuruga T, Oda K, Kawana K, Osuga Y, Fujii T.
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Journal Title
Cancer Sci.
Volume: 110
Issue: 10
Pages: 3068-3078
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Histone methyltransferase SMYD2 selective inhibitor LLY-507 in combination with poly ADP ribose polymerase inhibitor has therapeutic potential against high-grade serous ovarian carcinomas.2019
Author(s)
Kukita A, Sone K, Oda K, Hamamoto R, Kaneko S, Komatsu M, Wada M, Honjoh H, Kawata Y, Kojima M, Oki S, Sato M, Asada K, Taguchi A, Miyasaka A, Tanikawa M, Nagasaka K, Matsumoto Y, Wada-Hiraike O, Osuga Y, Fujii T
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Journal Title
Biochem Biophys Res Commun
Volume: in press
Issue: 2
Pages: 30555-8
DOI
Related Report
Peer Reviewed
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