| Project/Area Number |
16K07258
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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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| Research Field |
Molecular biology
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| Research Institution | Nihon University |
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Principal Investigator |
ARAI Naoto 日本大学, 生物資源科学部, 准教授 (70297795)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Rad52 / Rad51 / RecA / 相同組換え / 非相同末端結合 / 出芽酵母 / DNA末端結合 / DNA二本鎖切断修復 / DNA二本鎖切断 / DNA修復 / 遺伝子 |
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| Outline of Final Research Achievements |
Rad52 of budding yeast is essential to homologous recombination. DNA ligase catalyzes joining of DNA-end of linear plasmid DNA and produces circular DNA by intramolecular association. In the presence of Rad52, joining of DNA-end was enhanced and products that many linear DNA were tandemly jointed by intermolecular association were formed. For these activity of Rad52, both DNA binding sites in N-terminal and C-terminal regions of the Rad52 were required. When linear plasmid DNA was introduced in yeast cell, the ends of the linear DNA molecule are joined at by non-homologous end-joining and the plasmid DNA is retained in the cell. In rad52-deleted strain, retention of the plasmid DNA was reduced in to 1/4 of wild-type, suggesting that Rad52 is associated with non-homologous end joining.
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| Academic Significance and Societal Importance of the Research Achievements |
出芽酵母においてRad52は、DNAの二本鎖切断（DSB）傷害の相同組換えによる修復に必須であるが、本研究により非相同末端結合への関与が示唆された。このことは相同組換えと非相同末端結合が密接に関係することを示すものと考えられる。ヒトRad52には未解明な点が多いが、出芽酵母Rad52と構造上の類似点が多いため、非相同末端結合への関与が推測される。ヒトでは、DSBの修復のために非相同末端結合が主要経路であり、Rad52のさらなる研究によりDNA修復のエラーにより引き起こされるガンなどの疾患や病態 の解明、治療に新たな方向性を示すことが期待される。
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