Mechanism of a mismatch-repair-dependent quality-control system for homology-directed repair
| Project/Area Number |
17H01876
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | 相同性依存的修復 / ミスマッチ修復 / 染色体安定性 / DNA複製 / 一本鎖アニーリング / ツメガエル卵抽出液 / 試験管内系 / クロマチンリモデリング / DNA二重鎖切断 / Smarcad1 / Fun30 / 試験管内再構成 / DNA損傷修復 / 相同組換え / 二重鎖切断修復 / ツメガエル / 相同組み換え |
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| Outline of Final Research Achievements |
Homology-directed repair (HDR) is critical for the repair of DNA double-strand breaks, while HDR between similar but non-identical sequences can give rise to chromosome instability. The quality of HDR is maintained by the mismatch repair (MMR) pathway. However, the molecular mechanism of these reactions remains largely uncertain. In this study, we recapitulated an HDR reaction in Xenopus egg extracts, identified factors that maintain the accuracy of HDR, and studied the quality-control mechanism of HDR. We also discovered a novel mechanism that assists in the MMR reaction on chromatin. These studies contribute to the understanding of the MMR-dependent quality-control system for HDR and DNA replication.
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| Academic Significance and Societal Importance of the Research Achievements |
ゲノムの塩基配列情報の正確な継承と維持は生物にとって必須であるのみならず、ヒトの健康にも大きく関連する。本研究では、DNAの複製と、DNAの切断修復の二つの反応の正確性維持に重要な「ミスマッチ修復」システムの動作原理を、特に真核生物の染色体基本構造であるクロマチンに注目して解析し、新たなミスマッチ修復補助システムを同定するに至った。またDNA切断修復の正確性維持機構についても関与する因子の同定など、メカニズムの理解が進展した。これらの成果は、基礎生物学における学問的知見を発展させるのみならず、ゲノム不安定性に関連するヒト疾患の理解にも寄与する。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Regulation of mitotic recombination between DNA repeats in centromeres2017
Author(s)
Zafar,F., Okita,AK. Onaka,AT., Su,J., Katahira,Y., Nakayama,J. Takahashi,TS., Masukata, H., Nakagawa, T.
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Journal Title
Nucleic Acids Research
Volume: 44(22)
Pages: 11222-11235
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sensing and Processing of DNA Interstrand Crosslinks by the Mismatch Repair Pathway2017
Author(s)
Kato N, Kawasoe Y, Williams H, Coates E, Roy U, Shi Y, Beese LS, Scharer OD, Yan H, Gottesman ME, Takahashi TS, Gautier J.
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Journal Title
Cell Reports
Volume: 21
Pages: 1375-1385
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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