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Molecular mechanisms by which chromosomes regulate mitotic cell division and its relevance to causing human diseases

Research Project

Project/Area Number 16K21749
Research Category

Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)

Allocation TypeMulti-year Fund
Research Field Cell biology
Research InstitutionIbaraki National College of Technology (2018, 2020-2023)
ID Pharma (2019)

Principal Investigator

Yokoyama Hideki  茨城工業高等専門学校, 国際創造工学科, 准教授 (60397908)

Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥56,290,000 (Direct Cost: ¥43,300,000、Indirect Cost: ¥12,990,000)
Keywords細胞骨格・運動 / 分裂期 / 紡錘体 / 染色体分配 / 疾患誘導機序
Outline of Final Research Achievements

RECQL4 is mutated in Rothmund Thomson syndrome, characterized by cancer susceptibility. We find RECQL4 is a microtubule-associated protein (MAP) required for chromosome alignment to the metaphase plate. We detect that the patient cells, lacking RECQL4 protein, show chromosome misalignment, proposing that the chromosome misalignment may be the cause of the disease. We also find VPS72, one of the chromatin-remodeling complex proteins, is essential for postmitotic nuclear re-assembly. Mechanistically, VPS72 binds to postmitotic chromatin and incorporate a histone variant H2AZ on chromatin that enables to assemble compact and functional nuclei. SART1 is previously shown to be important for pre-mRNA splicing and mitotic progression, but the mitotic role of SART1 have not been characterized in detail. We identify SART1 is also a MAP localizing uniquely to spindle poles. We show SART1 mechanistically recruits pericentriolar material proteins and contributes to spindle pole assembly.

Academic Significance and Societal Importance of the Research Achievements

ロスムンド・トムソン症候群の原因タンパク質RECQL4の新たな機能と、疾患の誘導メカニズムを提案することができた。また細胞分裂などの過程に比べて十分に研究されていない核の再形成に、VPS72依存的なH2AZの取り込みが重要であることを解明できた。さらにSART1のこれまでに例のない局在の仕方(SART1キャップ)と紡錘体極の成熟での機能を発見。これらの時期・場所特異的な機能はin vitroやヒト培養細胞に加えて、カエル卵抽出液を使った再構成系を用いたからこそ得られた成果である。今後これらの知見や研究ツールを用いて、研究分野また当研究室でのさらなる研究の展開が期待できる。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (6 results) Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Open Access: 4 results,  Peer Reviewed: 2 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Int'l Joint Research] アーヘン大学/ボン大学/マックスプランク研究所(ドイツ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] アーヘン大学/ボン大学/マックスプランク研究所(ドイツ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] ボン大学/アーヘン大学/マックスプランク研究所(ドイツ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] アーヘン大学/ボン大学/マックスプランク研究所(ドイツ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] マックスプランク研究所/アーヘン大学/ボン大学(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] マックスプランク研究所/アーヘン大学/ボン大学(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] SART1 localizes to spindle poles forming a SART1 cap and promotes spindle pole assembly2023

    • Author(s)
      Yokoyama Hideki、Moreno-Andr?s Daniel、Takizawa Kaoru、Chu Zhenzhen、Scheufen Anja、Funabashi Tsumugi、Ma Jian、Antonin Wolfram、Gruss Oliver J.、Haramoto Yoshikazu
    • Journal Title

      bioRxiv

      Volume: 1 Pages: 1-27

    • DOI

      10.1101/2023.10.27.564116

    • Related Report
      2023 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] SART1 localizes to spindle poles forming a SART1 cap and promotes centrosome and spindle assembly.2021

    • Author(s)
      Takizawa K, Ma J, Moreno-Andrés D, Antonin W, Haramoto Y, Yokoyama H (corresponding author)
    • Journal Title

      Research Square

    • DOI

      10.21203/rs.3.rs-126500/v1

    • Related Report
      2020 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis2020

    • Author(s)
      Moreno-Andres Daniel、Yokoyama Hideki、Scheufen Anja、Holzer Guillaume、Lue Hongqi、Schellhaus Anna Katharina、Weberruss Marion、Takagi Masatoshi、Antonin Wolfram
    • Journal Title

      Cells

      Volume: 9 Issue: 7 Pages: 1702-1702

    • DOI

      10.3390/cells9071702

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chromosome alignment requires the MAP RECQL4, mutated in the Rothmund-Thomson syndrome2019

    • Author(s)
      Yokoyama H, Moreno-Andres D, Astrinidis SA, Hao Y, Weberruss M, Lue H, Haramoto Y, Gruss OJ, and Antonin W.
    • Journal Title

      Life Science Alliance

      Volume: 2 Issue: 1 Pages: e201800120-e201800120

    • DOI

      10.26508/lsa.201800120

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] SART1は紡錘体極の最末端に局在、中心体マトリックスタンパク質を集積させ極を形成する2023

    • Author(s)
      横山英樹、船橋紬
    • Organizer
      日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 無細胞タンパク質分解系を用いた遺伝子として扱える人工抗体様タンパク質の開発2023

    • Author(s)
      遠藤愛実, 武藤将正, 横山英樹
    • Organizer
      日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] NOC4Lは紡錘体の二極性形成と分裂の進行に関わる2022

    • Author(s)
      小川 健, 西野 日菜, 横山 英樹
    • Organizer
      日本化学会関東支部茨城地区研究交流会
    • Related Report
      2022 Research-status Report
  • [Presentation] PABPN1は紡錘体の二極化を保証する2022

    • Author(s)
      中村 寛大, 西野 日菜, 横山 英樹
    • Organizer
      日本化学会関東支部茨城地区研究交流会
    • Related Report
      2022 Research-status Report
  • [Presentation] 武藤 将正, 横山 英樹2022

    • Author(s)
      抗体様タンパク質による細胞内タンパク質分解法の開発
    • Organizer
      日本化学会関東支部茨城地区研究交流会
    • Related Report
      2022 Research-status Report
  • [Presentation] SART1 の N 末端微小管結合ドメインが紡錘体形成に必要2022

    • Author(s)
      梶間 睦生, 船橋 紬, 横山 英樹
    • Organizer
      日本化学会関東支部茨城地区研究交流会
    • Related Report
      2022 Research-status Report
  • [Presentation] VPS72 and its function loading H2A. Z on chromatin are essential for postmitotic nuclear assembly and function2019

    • Author(s)
      Hideki Yokoyama, Daniel Moreno-Andres, Wolfram Antonin
    • Organizer
      日本分子生物学会(双方修正依頼済10/26増田様)
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] カエル卵抽出液を使って細胞核形成機構に迫る : Histone H2A. Zの役割2019

    • Author(s)
      横山英樹
    • Organizer
      XCIJ-MA研究集会(双方修正依頼済10/26増田様)
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] カエル卵抽出液を使った細胞周期研究 : 早老症原因遺伝子RECQL4の機能2019

    • Author(s)
      横山英樹
    • Organizer
      XCIJ-MA 研究集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Mitotic chromosome congression requires the microtubule- associated protein RECQL4, mutated in the Rothmund-Thomson syndrome2018

    • Author(s)
      Hideki Yokoyama
    • Organizer
      International Xenopus Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2017-04-24   Modified: 2025-01-30  

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