| Project/Area Number |
18K18191
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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 63020:Radiation influence-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Yasuhara Takaaki 東京大学, 大学院医学系研究科(医学部), 助教 (90757056)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Discontinued (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | R-loop構造 / DNA二重鎖切断 / DNA損傷シグナリング / DNA修復 |
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| Outline of Final Research Achievements |
In this study, we revealed that R-loops, a special structure consisting of DNA and RNA, are formed when DNA double-strand breaks are induced in the transcribed genomic regions. Moreover, recognition of R-loops by Rad52 promotes the activation of the accurate repair pathway, or homologous recombination repair, a mechanism designated as Transcription-Associated Homologous Recombination Repair (TA-HRR). Furthermore, we demonstrated that inhibiting TA-HRR significantly increased interchromatid fusions, a precursor of genomic abnormalities frequently observed in cancer, suggesting that TA-HRR is critical for suppressing cancer development.
These findings represent an inherent mechanism by which human cells suppress cancer development. Detailed understanding of these kinds of protection mechanisms in human cells and how the collapse of these mechanisms leads to development of diseases may pave the way for finding a novel target to develop new drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
今回明らかになった転写共役型相同組換え修復のメカニズムは、ゲノム異常を原因として生じるがんなどの疾患を防ぐために細胞が保持している防御機構の一つであり、それらの破綻は疾患の発症と密接に関連していることが示唆された。このようなメカニズムの解明によって将来的には、疾患を予防したり、治療したりする手法の開発につながると考えられる。
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