2023 Fiscal Year Final Research Report
Cellular responses to DNA double-strand breaks caused by transcription stress
| Project/Area Number |
21K12245
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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 63020:Radiation influence-related
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
SAKASAI Ryo 金沢医科大学, 医学部, 准教授 (10549950)
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| Co-Investigator(Kenkyū-buntansha) |
西 良太郎 東京工科大学, 応用生物学部, 准教授 (80446525)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | DNA二本鎖切断 / 転写 / カンプトテシン |
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| Outline of Final Research Achievements |
Transcriptional stress induced by the anti-cancer drug camptothecin (CPT) is known to cause DNA double-strand breaks (transcription-coupled DSBs, tc-DSBs), but the mechanisms of tc-DSB generation and repair have not been well understood. We analyzed tc-DSB response by focusing on RecQL5, a DNA helicase, which suggests that DNA secondary structures related to the DNA-RNA hybrid are induced in the vicinity of stalled transcription machinery, but in RecQL5-deficient cells, the DNA secondary structures are not resolved and leads the involvement of another DNA repair TC-NER, resulting in tc-DSB generation.
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| Free Research Field |
細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、抗がん剤であるCPTによる細胞影響において、あまり研究が進んでいない転写に対する影響に注目したものである。転写は全ての細胞で起こっており、転写ストレス応答の解明は、CPT誘導体を用いた化学療法における副作用を考える上で重要と考えられる。また、Top1-DPCの代謝異常は神経変性疾患との関連が言われており、本研究の成果はTop1-DPCが神経細胞で毒性を発揮する機構を示唆するもので、神経疾患の病態解明にもつながる可能性がある。
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