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Mechanism of a mismatch-repair-dependent quality-control system for homology-directed repair

Research Project

Project/Area Number 17H01876
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionKyushu University

Principal Investigator

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

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
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)
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
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (21 results)

All 2019 2018 2017 Other

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (13 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Remarks (3 results)

  • [Journal Article] Heterochromatin suppresses gross chromosomal rearrangements at centromeres by repressing Tfs1/TFIIS-dependent transcription2019

    • Author(s)
      Okita Akiko K.、Zafar Faria、Su Jie、Weerasekara Dayalini、Kajitani Takuya、Takahashi Tatsuro S.、Kimura Hiroshi、Murakami Yota、Masukata Hisao、Nakagawa Takuro
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1 Pages: 17-17

    • DOI

      10.1038/s42003-018-0251-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nucleosomes around a mismatched base pair are excluded via an Msh2-dependent reaction with the aid of SNF2 family ATPase Smarcad1.2018

    • Author(s)
      Terui R, Nagao K, Kawasoe Y, Taki K, Higashi TL, Tanaka S, Nakagawa T, Obuse C, Masukata H, Takahashi TS
    • Journal Title

      Genes & development

      Volume: 32(11-12) Issue: 11-12 Pages: 806-821

    • DOI

      10.1101/gad.310995.117

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shelterin promotes tethering of late replication origins to telomeres for replication‐timing control2018

    • Author(s)
      Ogawa Shiho、Kido Sayuri、Handa Tetsuya、Ogawa Hidesato、Asakawa Haruhiko、Takahashi Tatsuro S、Nakagawa Takuro、Hiraoka Yasushi、Masukata Hisao
    • Journal Title

      The EMBO Journal

      Volume: 37 Issue: 15 Pages: 15-15

    • DOI

      10.15252/embj.201898997

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
  • [Presentation] 真核生物 DNA ミスマッチ修復機構による遺伝情報維持反応の解析2019

    • Author(s)
      高橋達郎
    • Organizer
      国立遺伝学研究所・研究集会「染色体安定維持研究会」
    • Related Report
      2019 Annual Research Report
  • [Presentation] クロマチン構造上でのDNAミスマッチ修復を促進するメカニズム2019

    • Author(s)
      高橋達郎
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ミスマッチ塩基に依存したクロマチンリモデリングの試験管内再構成2019

    • Author(s)
      高橋達郎
    • Organizer
      第25回複製・組換え・修復ワークショップ
    • Related Report
      2019 Annual Research Report
  • [Presentation] Reconstitution of a chromatin-remodeling reaction that facilitates post-replicative DNA mismatch repair2019

    • Author(s)
      高橋達郎
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The quality control mechanism of homology-directed repair in Xenopus egg extracts2019

    • Author(s)
      高橋達郎
    • Organizer
      CHROMOSOME DYNAMICS, An international symposium on chromatin and chromosome stability
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ミスマッチ塩基に依存したヌクレオソームリモデリングの試験管内再構成2019

    • Author(s)
      高橋達郎
    • Organizer
      第37回染色体ワークショップ・第18回核ダイナミクス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 真核生物ミスマッチ修復の多様な動作を支える分子基盤2019

    • Author(s)
      高橋達郎
    • Organizer
      国立遺伝学研究所・研究集会「ゲノムの維持継承を支える分子基盤の包括的理解とその発展」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Msh2-dependent regulation of single-strand annealing between divergent sequences in Xenopus egg extracts2018

    • Author(s)
      高橋達郎
    • Organizer
      The 11th 3R+3C Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ミスマッチ修復システムに依存した抗組換え反応の試験管内再現による解析2018

    • Author(s)
      高橋達郎
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 相同性依存的修復の品質管理機構を試験管内再現系によって探る2018

    • Author(s)
      高橋達郎
    • Organizer
      第3回ゲノム編集学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [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
  • [Remarks] 研究室ウエブサイト

    • URL

      http://www.biology.kyushu-u.ac.jp/~chromosome/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 研究室web site

    • URL

      http://www.biology.kyushu-u.ac.jp/~chromosome/top.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] プレスリリース

    • URL

      https://www.kyushu-u.ac.jp/f/33515/18_06_22_jp.pdf

    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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