2023 Fiscal Year Final Research Report
Study of RecQ4 function in DNA repair pathway choice
| Project/Area Number |
21K06551
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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 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Toho University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | DNA修復 / RecQ4 / 非相同末端結合 / 相同組換え |
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| Outline of Final Research Achievements |
In this study, we investigated the function of RecQ4 to clarify the mechanism of DNA double-strand break (DSB) repair pathway choice. The two pathways are known to be involved in DSB repair: non-homologous end-joining, which is initiated by Ku70/Ku80 complex, and homologous recombination, which is initiated by MRE11. Our results suggest that the N-terminal fragment of RecQ4 inhibited both the Ku70/Ku80 complex formation and the endonuclease activity of MRE11. RecQ4 may affect the DSB repair pathway choice through its N-terminal domain.
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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 |
本研究結果により、RecQ4がN末側領域を介して非相同末端結合と相同組換えを促進または抑制する経路選択機能を有する可能性が示された。これはDNA修復経路の選択における新たなメカニズムの発見および、DNA修復と関連性が高い発がんや老化のメカニズムの理解へと繋がる。さらに、DNA修復経路の阻害薬の開発へと応用でき、がん治療における放射線照射や化学療法剤などの治療効果の向上に貢献できる。また、DNA二本鎖切断修復を利用した遺伝子改変技術であるゲノム編集の効率上昇を介して遺伝子治療分野の発展にも寄与する。
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