| Project/Area Number |
18K06173
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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 43040:Biophysics-related
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| Research Institution | National Institutes for Quantum and Radiological Science and Technology |
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Principal Investigator |
Ishida Hisashi 国立研究開発法人量子科学技術研究開発機構, 量子生命科学領域, 上席研究員(定常) (60360418)
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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: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | ヌクレオソーム / DNA / 構造変化 / 遺伝子発現 / ねじれ / 分子動力学シミュレーション / 自由エネルギー計算 / DNA解離 / ヒストン / 自由エネルギー |
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| Outline of Final Research Achievements |
The free energy calculations using molecular dynamics simulations showed that DNA dissociation of CENP-A nucleosomes in the chromosomal centromere region is more likely to occur than that of canonical nucleosomes. Furthermore, a molecular dynamics simulation was performed in which a force imitating the twisting force generated by RNA polymerase was applied to both ends of the canonical nucleosome DNA. The results indicated that when a left-handed twisting force was applied, the DNA was easily dissociated from the histone, and conversely, when a right-handed twisting force was applied, the DNA was difficult to be dissociated from the histone. These were found to be caused by the geometrical property of the DNA double helix structure and the physical characteristics of DNA such as flexibiity and bendability.
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| Academic Significance and Societal Importance of the Research Achievements |
ヌクレオソームのDNAに作用するねじれの力が、ヌクレオソームの大規模な構造変化を引き起こすことがわかった。その分子論的原因は、DNAが右巻きのらせんの形をしている幾何学的特性とDNA固有の物性的特性（柔らかさ、曲がりやすさ）に起因することがわかった。このことはヌクレオソーム構造変化を伴う複雑な遺伝子発現メカニズムが「DNAのらせん構造」と「ねじれの力の向き」といった単純な仕組みによっても調節されている可能性を示している。本研究は、分子動力学シミュレーション法を最大限に活用したヌクレオソームの機能発現メカニズムの解析であり、将来的に遺伝子発現機構の全容解明につながる。
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