2023 Fiscal Year Final Research Report
Investigation of mechanisms and biological roles of homologous recombination.
Project/Area Number |
20K12166
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 63020:Radiation influence-related
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Research Institution | Oita University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
西田 欣広 大分大学, 医学部, 准教授 (10336274)
寺林 健 大分大学, 医学部, 准教授 (40452429)
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Project Period (FY) |
2020-04-01 – 2024-03-31
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Keywords | 相同組換え |
Outline of Final Research Achievements |
Homologous recombination is one of the DNA repair mechanisms that repair double-strand breaks in genes. In eukaryotes, the mechanism of homologous recombination has been poorly understood, especially regarding the mechanism of the latter half of homologous recombination. In this study, we addressed how recombination intermediates were resolved by the structure-specific endonuclease. On the other hand, to analyze the site of double-strand breaks that occur secondary to failure of homologous recombination, double-strand breaks are separated by pulsed field electrophoresis and DNA is recovered from the gel. Then the sequence of its terminal portion has been comprehensively analyzed by the next generation sequencer. We are currently developing a method for determining the sequence of the terminal portion of recovered DNA, and plan to write a paper if we can prove the specificity and reproducibility of this method.
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Free Research Field |
分子生物学
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Academic Significance and Societal Importance of the Research Achievements |
相同組換えの異常は、DNAの二重鎖切断の修復に支障をきたすため、染色体異常の原因となる。その結果、臓器の機能不全やがんの原因となる。実際、その機能に問題を生じた場合、ファンコニ貧血や遺伝性乳癌卵巣癌症候群を引き起こす。一方、哺乳類では相同組換えは細胞の生存に必須の生命現象であり、その機能を阻害することで細胞は死んでしまう。さらに相同組換えは増殖細胞で活性が高いことも知られている。このことから相同組換えを標的とした阻害物質が抗がん剤として活用できる可能性が高く、一部でそのような物質が実用化され始めている。このような薬剤の開発のために、相同組換えのメカニズムを解明することが重要である。
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