Project/Area Number |
18K06191
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 43050:Genome biology-related
|
Research Institution | Hamamatsu University School of Medicine (2020-2021) Nagoya University (2018-2019) |
Principal Investigator |
IIJIMA Kenta 浜松医科大学, 光尖端医学教育研究センター, 研究技術職員 (20565626)
|
Project Period (FY) |
2018-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | LINE-1 / DNA損傷 / がん化 / 発がん / DNA損傷応答 / 細胞老化 / レトロトランスポゾン |
Outline of Final Research Achievements |
Retrotransposition of Long interspersed element-1 (LINE-1) is induced by various stimuli, however, the precise mechanism and its biological roles remain unknown. The improvement of analysis to comprehensively identify the de novo integrations of LINE-1 showed the unexpectedly higher frequencies in tumor tissues, implying the intimate association of tumor progression and LINE-1 retrotransposition. In this study, we found that LINE-1-integration directed to a specific region was provoked by DNA damage induction. The interaction between LINE-1 protein complex and transcriptional factors , which response to DNA damage and accumulate on the target genes underlay the region directional LINE-1 retrotransposion.
|
Academic Significance and Societal Importance of the Research Achievements |
本研究ではDNA損傷により誘導される部位特異的なLINE-1転移誘導機構、および選択的な細胞形質変化の可能性を明らかにした。本研究成果は基礎生物学のみにとどまらず、医薬学領域にも広範な影響をもたらす。すなわち、LINE-1の活性化状態により疾患のリスク評価に応用できる可能性、あるいはLINE-1活性の適切な制御を可能とする新規薬剤の開発により、がんをはじめとした疾患の予防・治療が可能となると期待され、本研究によりもたらされる知見は今後の医療・創薬分野における新たな創造的基盤をもたらすものと予想される。
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