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A unified understanding of replication error correction and antirecombination mediated by the mismatch repair system

Research Project

Project/Area Number 16K14671
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Molecular biology
Research InstitutionKyushu University

Principal Investigator

Takahashi Tatsuro  九州大学, 理学研究院, 准教授 (50452420)

Research Collaborator Oda Satomi  
Kawasoe Yoshitaka  
Sakazume Aya  
Terui Riki  
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsミスマッチ修復 / 相同組換え / ツメガエル卵抽出液 / 無細胞系 / DNA二重鎖切断損傷 / 相同性依存的修復 / 突然変異 / ゲノム安定性 / 相同組み換え / DNA修復 / DNA組換え
Outline of Final Research Achievements

The mismatch repair system not only increases the replication fidelity by correcting replication errors but also improves the recombination fidelity by preventing illegitimate recombination. To study how these reactions are branched and how illegitimate recombination is inhibited, we established an in vitro model system that recapitulates the inhibition of recombination between divergent sequences. We induced single-strand annealing repair of DNA double-strand breaks by adding DNA substrates into nucleoplasmic extracts of Xenopus eggs and found that sequence divergence between the annealing units significantly reduces the annealing reaction. We also found that the mismatch-recognition complex and a RecQ-family helicase prevent annealing of divergent sequences. This system will be useful to study the recombination intermediates and factors that are involved in the inhibition of illegitimate recombination.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] Regulation of mitotic recombination between DNA repeats in centromeres.2017

    • Author(s)
      Zafar,F., Okita,AK. Onaka,AT., Su,J., Katahira,Y., Nakayama,J. Takahashi,TS., Masukata, H., Nakagawa, T.
    • Journal Title

      Nucleic Acids Research

      Volume: 44(22) Issue: 19 Pages: 11222-11235

    • DOI

      10.1093/nar/gkx763

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sensing and Processing of DNA Interstrand Crosslinks by the Mismatch Repair Pathway.2017

    • 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.
    • Journal Title

      Cell Reports

      Volume: 21 Issue: 5 Pages: 1375-1385

    • DOI

      10.1016/j.celrep.2017.10.032

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MutSα maintains the mismatch repair capability by inhibiting PCNA unloading2016

    • Author(s)
      Kawasoe, Y., Tsurimoto, T., Nakagawa, T., Masukata, H., Takahashi, TS.
    • Journal Title

      eLIFE

      Volume: 12;5

    • DOI

      10.7554/elife.15155

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] PCNA Retention on DNA into G2/M Phase Causes Genome Instability in Cells Lacking Elg12016

    • Author(s)
      Catherine Johnson, Vamsi K. Gali, Tatsuro S. Takahashi, Takashi Kubota
    • Journal Title

      Cell Reports

      Volume: 16 Issue: 3 Pages: 684-695

    • DOI

      10.1016/j.celrep.2016.06.030

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ミスマッチ修復依存的なヘテロ二重鎖解消反応の試験管内解析2017

    • Author(s)
      高橋 達郎
    • Organizer
      第34回染色体ワークショップ・第15回核ダイナミクス研究会
    • Place of Presentation
      千葉県木更津市
    • Year and Date
      2017-01-11
    • Related Report
      2016 Research-status Report
  • [Presentation] An in vitro model system for functional interaction of mismatch repair with chromatin assembly and homology-directed repair2017

    • Author(s)
      Tatsuro Takahashi
    • Organizer
      The 6th US-Japan DNA Repair Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] In vitro analysis of the mismatch-repair-dependent anti-recombination reaction2017

    • Author(s)
      高橋 達郎
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 類似配列間の相同性依存的組換えを抑制する反応の試験管内再現2017

    • Author(s)
      高橋 達郎
    • Organizer
      第35回染色体ワークショップ・第16回核ダイナミクス研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] In vitro analysis of interplay between chromatin replication, homology-directed repair, and mismatch repair2016

    • Author(s)
      高橋 達郎
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Interplay between DNA synthesis, chromatin assembly, and mismatch repair2016

    • Author(s)
      高橋 達郎
    • Organizer
      The 10th 3R symposium
    • Place of Presentation
      島根県松江市
    • Year and Date
      2016-11-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ミスマッチ修復による相同組み換え制御の試験管内解析2016

    • Author(s)
      高橋 達郎
    • Organizer
      国立遺伝学研究所・研究集会「生物ゲノム安定性の分子機構」
    • Place of Presentation
      静岡県三島市
    • Year and Date
      2016-10-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Chromatin remodeling facilitates eukaryotic mismatch repair by promoting the displacement of nucleosomes around mismatches2016

    • Author(s)
      高橋 達郎
    • Organizer
      At the Intersection of DNA Replication and Genome Maintenance: from Mechanisms to Therapy
    • Place of Presentation
      Trieste, Italy
    • Year and Date
      2016-06-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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