| Project/Area Number |
17K15065
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Molecular biology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | DNA複製 / テロメア / ORC / TRF2 / 染色体安定性 / 複製ストレス |
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| Outline of Final Research Achievements |
Telomeres are essential structures that protect the ends of human chromosomes but are also known as“difficult-to-replicate”regions. In this study, we aimed to clarify the mechanism by which origin recognition complex (ORC) binds to telomeric repeat binding factor 2 (TRF2) and to assess the biological significance of the ORC-TRF2 interaction using a separation-of-function mutant of TRF2. Our study using cells harboring the TRF2 E111A/E112A mutant deficient only in the ORC-binding suggests that TRF2 binding to ORC contributes to the ORC recruitment and chromosomal stability at telomeres.
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| Academic Significance and Societal Importance of the Research Achievements |
1) TRF2-ORC結合様式を詳細に解析した結果、ORC結合能を特異的に欠損したTRF2変異体の創出に成功した。2) 変異体の置換型ヒト培養細胞株を樹立することで、テロメアへのORCリクルートを特異的に阻害し、その生理的重要性を厳密に解析した。その結果、TRF2依存性ORCリクルートがテロメア染色体の安定性に寄与することを世界で初めて明らかにした。3) ORCリクルートとテロメア恒常性制御の密接なつながりを示唆したこれらの成果は、ゲノム不安定性を示すがん等の疾患の原因究明および治療法開発の強化につながることが期待できる。
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