| Project/Area Number |
18K06180
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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 43050:Genome biology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ゲノム / DNA損傷 / レトロトランスポゾン / 転移因子 / LINE-1 / DNA修復 / トランスポゾン / ゲノム維持 / L1 |
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| Outline of Final Research Achievements |
Human LINE-1 retrotransposons still continue to generate inter- or intra-genetic diversity by mobilizing their own sequences into other genomic loci termed retrotransposition. Although more than one hundred disease-causing mutations by LINE-1 retrotransposition have been reported., the mechanisms of LINE-1 retrotransposition require elucidation. In this study, we demonstrated that 1) multiple DNA repair factors interact with the LINE-1 encoded proteins, 2) LINE1 proteins are posttranslationally modified by these DNA repair factors identified, and 3) PARP2 acts as a sensor protein that detect the sites of LINE-1 retrotransposition and plays a role in LINE-1 retrotransposition. These data suggest that LINE-1 retrotransposition can be effectively suppressed by an inhibitor that modulate activities of these DNA repair factors.
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| Academic Significance and Societal Importance of the Research Achievements |
LINE-1による転移は、生殖細胞、初期発生、神経前駆細胞や多くのがん細胞など、様々な場所・タイミングでおこる。疾患につながる変異につながることを除けば、LINE-1の生物学的な意味はまだ理解されていない。本研究では、宿主細胞とLINE-1との相互作用からその転移機構の一端を明らかにした。これによりLINE-1の人為的な操作を行えるだけでなく、LINE-1が宿主にどうのような影響をもたらたすのか、その本質に迫る研究へと発展することができるだろう。将来的には、我々のゲノムがどのように形成されてきたのかを検証し、また今後どのように変化していくのかを予測することにもつながると期待される。
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