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Biochemical characterizations of the cohesin ring for understanding the establishment mechanism of sister chromatid cohesion

Research Project

Project/Area Number 16H06160
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Molecular biology
Research InstitutionNational Institute of Genetics (2017-2018)
Tokyo Institute of Technology (2016)

Principal Investigator

MURAYAMA Yasuto  国立遺伝学研究所, 新分野創造センター, 准教授 (60531663)

Research Collaborator KODERA Noriyuki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2017: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2016: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Keywords染色体動態 / 染色体分配 / 姉妹染色分体間接着 / SMC複合体 / コヒーシン / 試験管内再構成 / 姉妹染色体接着 / ゲノム / 蛋白質 / 生化学 / SMC 複合体
Outline of Final Research Achievements

Cohesin is a ring-shaped, multisubunit ATPase that topologically encircles DNA. The ring complex makes vital contributions to sister chromatid cohesion and global chromosomal organization to regulate numerous chromosomal events including chromosome segregation, DNA repair and transcriptional regulations. How cohesin establishes these chromosomal structures by topological DNA embrace is poorly understood. Here we found that purified cohesin mediates DNA-DNA interactions by single-stranded DNA (ssDNA)-dependent mechanism. Our genetic analyses have also suggested that ssDNA region plays important roles for establishment of sister chromatid cohesion. This study unveiled a novel cohesin’s activity and provides mechanistic insight into establishment of sister chromatid cohesion.

Academic Significance and Societal Importance of the Research Achievements

染色体分配に不可欠であることに加え、コヒーシンは間期染色体のグローバルな高次構造形成も制御し、転写制御を介して分化・発生にも関与することが次々と判明している。また、様々な染色体機能が明らかになる中、その機能異常が染色体異常疾患や不妊等と関連することが報告されている。本研究は、精製コヒーシンのDNA結合活性を直接解析することで動作機構の一端を明らかにした。得られた知見は、基礎研究への貢献に加え、長期的展望として人類の健康増進に資する研究につながると期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (21 results)

All 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (9 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Remarks (3 results)

  • [Int'l Joint Research] フランシスクリック研究所(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] フランシスクリック研究所(英国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments2018

    • Author(s)
      Murayama Yasuto
    • Journal Title

      Nucleus

      Volume: 9 Issue: 1 Pages: 492-502

    • DOI

      10.1080/19491034.2018.1516486

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of DNA-DNA Interactions by the Cohesin Ring2018

    • Author(s)
      Murayama Yasuto、Samora Catarina P.、Kurokawa Yumiko、Iwasaki Hiroshi、Uhlmann Frank
    • Journal Title

      Cell

      Volume: 172 Issue: 3 Pages: 465-477

    • DOI

      10.1016/j.cell.2017.12.021

    • NAID

      120007117667

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two three-strand intermediates are processed during Rad51-driven DNA strand exchange.2018

    • Author(s)
      Ito K, Murayama Y, Takahashi M, Iwasaki H.
    • Journal Title

      Nat Struct Mol Biol

      Volume: 25 Issue: 1 Pages: 29-36

    • DOI

      10.1038/s41594-017-0002-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis.2017

    • Author(s)
      Argunhan B, Leung WK, Afshar N, Terentyev Y, Subramanian VV, Murayama Y, Hochwagen A, Iwasaki H, Tsubouchi T, Tsubouchi H.
    • Journal Title

      EMBO J

      Volume: 36 Issue: 17 Pages: 2488-2509

    • DOI

      10.15252/embj.201695895

    • NAID

      120007117670

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In vitro site-specific recombination mediated by the tyrosine recombinase XerA of Thermoplasma acidophilum.2017

    • Author(s)
      Jo M, Murayama Y, Tsutsui Y and Iwasaki H.
    • Journal Title

      Genes to Cells

      Volume: 印刷中 Issue: 7 Pages: 646-661

    • DOI

      10.1111/gtc.12503

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 1.The Differentiated and Conserved Roles of Swi5-Sfr1 in Homologous Recombination.2017

    • Author(s)
      Argunhan B, Murayama Y and Iwasaki H.
    • Journal Title

      FEBS letter

      Volume: - Issue: 14 Pages: 2035-2047

    • DOI

      10.1002/1873-3468.12656

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structure of the cohesin loader Scc22017

    • Author(s)
      William C. H. Chao, Yasuto Murayama, Sofia Munoz, Andrew W. Jones, Benjamin O. Wade, Andrew G. Purkiss, Xiao-Wen Hu, Aaron Borg, Ambrosius P. Snijders, Frank Uhlmann, Martin R. Singleton
    • Journal Title

      nature COMMUNICATIONS

      Volume: - Issue: 1

    • DOI

      10.1038/ncomms13952

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] DNA binding by the Mis4 loader exerts a stimulatory effect on cohesin2018

    • Author(s)
      Yasuto Murayama
    • Organizer
      DMBO EMBL Symposia: Principles of Chromosome Structure and Function
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNA binding ability of the cohesin loader stimulates topological DNA entrapment by the cohesin ring2018

    • Author(s)
      Yasuto Murayama
    • Organizer
      3R & 3C Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cohesin mediates DNA-DNA tethering in vitro2017

    • Author(s)
      Yasuto Murayama, Catarina P. Samara, Frank Uhlmann.
    • Organizer
      The 2nd meeting on SMC proteins. Chromosome organizers from bacteria to human
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 試験管内再構成から予想される姉妹染色体接着の形成メカニズム2017

    • Author(s)
      村山泰斗
    • Organizer
      平成29年度 若手放射線生物学研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] コヒーシンリングによる姉妹染色体接着形成メカニズムの解明2017

    • Author(s)
      村山泰斗
    • Organizer
      日本遺伝学会 第89回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] コヒーシン複合体は2本のDNAと同時に結合する2017

    • Author(s)
      村山泰斗
    • Organizer
      第24回 DNA複製・組換え・修復ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] 姉妹染色体接着はどのように形成されるか?2017

    • Author(s)
      村山泰斗
    • Organizer
      2017年度 生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 精製したコヒーシンはATP依存的に2本のDNAと結合する2017

    • Author(s)
      村山泰斗
    • 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 合同開催
    • Related Report
      2017 Annual Research Report
  • [Presentation] The same elementary reaction can dirve both DNA entry into and exit out of the chromosomal cohesin ring2016

    • Author(s)
      Yasuto Murayama, Frank Uhlmann
    • Organizer
      The 10th 3R Symposium
    • Place of Presentation
      ホテル一畑(島根県松江市)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 国立遺伝学研究所

    • URL

      https://www.nig.ac.jp/nig/ja/research/organization-top/laboratories/murayama

    • Related Report
      2018 Annual Research Report
  • [Remarks] 研究室紹介

    • URL

      https://www.nig.ac.jp/nig/ja/research/organization-top/laboratories/murayama

    • Related Report
      2017 Annual Research Report
  • [Remarks] IWASAKA Laboratory

    • URL

      http://www.iwasakilab.bio.titech.ac.jp

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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