2018 Fiscal Year Final Research Report
Understanding the mechanisms by which a replisome component Ctf4 promotes proper repair of DNA double-strand breaks at arrested replication forks
| Project/Area Number |
17K15160
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Genetics/Chromosome dynamics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Sasaki Mariko 東京大学, 定量生命科学研究所, 助教 (50722013)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | DNA複製阻害 / DNA二本鎖切断 / Ctf4 / ゲノム再編成 / ゲノム不安定化 / rDNA |
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| Outline of Final Research Achievements |
In this study, I aimed to understand the molecular mechanisms by which Ctf4 protein promotes proper repair of DNA double-strand breaks (DSBs) formed upon replication inhibition. To this end, I compared the levels of replisome factors and homologous recombination factors bound around DSBs by chromatin immunoprecipitation and identified factors whose association levels are altered in the absence of Ctf4. Furthermore, I identified the Ctf4-interacting protein that may function together with Ctf4 during DSB repair. I will examine in a future study how these factors collaborate together with Ctf4 to regulate DSB repair.
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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 |
DNA複製は、遺伝情報を正確に伝達するために必須である。しかし複製装置の進行はゲノム上の様々な障害によって止まる。複製阻害が起きると、最も危険なDNA損傷であるDNA二本鎖切断（DNA double-strand break, DSB）ができやすくなりゲノム不安定化が誘導されるが、その修復機構は不明である。申請者は先行研究から、複製装置の構成因子であるCtf4タンパク質がDSB修復に必要であることを明らかにした。本研究課題ではCtf4タンパク質の作用過程やDSB修復時に必要なパートナー因子を明らかにしたことから、Ctf4タンパク質の作用機構を探る上で重要な成果を得ることができた。
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