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Study of the mechanism of regulation of circular chromosome stability conserved in yeast and human

Research Project

Project/Area Number 17K07502
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Genetics/Chromosome dynamics
Research InstitutionHiroshima University

Principal Investigator

Ueno Masaru  広島大学, 統合生命科学研究科(先), 准教授 (90293597)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsテロメア / 分裂酵母 / ヒト細胞 / 環状染色体 / 抗癌剤 / 抗がん剤 / EVウイルス / がん / DNA修復 / 染色体分配 / 遺伝病 / ヒト培養細胞
Outline of Final Research Achievements

Ring chromosomes have association with some genetic disorders and cancers. In Schizosaccharomyces pombe, lack of Pot1 results in survivors with circular chromosomes. Therefore pot1 disruptant is suitable to study how cells with circular chromosomes survive and how circular chromosomes are maintained. Fission yeast Cut17/Bir1, Ark1, Pic1, and Nbl1 is a conserved chromosome passenger complex (CPC) functioning mainly throughout mitosis. We found that CPC is synthetically lethal in combination with pot1. We also obtained a novel pik1 mutant, pik1-1, which is synthetically lethal with pot1. We found that pik1-1 mutation does not affect chromosome circularization. Thus, our results suggest that pik1 is required for the maintenance of circular chromosomes. We also found that strains with circular chromosomes, due to loss of pot1,require the 9-1-1 complex for their growth in the presence of DNA replication inhibitor.

Academic Significance and Societal Importance of the Research Achievements

本研究で見つかった分裂酵母の環状染色体の維持に関与する因子は、ヒトでも同様の機能があることが期待できる。その場合、本研究の成果を利用すると、a)環状染色体を安定化することで、環状染色体を持つ遺伝病患者のがんのリスクを軽減したり、b)環状染色体を不安定化することで、環状染色体を持つがん細胞を選択的に死滅させる新しい抗がん剤の開発につながる可能性があり、がんの予防や治療への貢献が期待できる。

Report

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

    (21 results)

All 2019 2018 2017 Other

All Int'l Joint Research (7 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] Beni-Sueo University(エジプト)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Sussex(英国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Sussex(英国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Beni-Suef University(エジプト)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Sussex(英国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Beni-Suef University(エジプト)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2017 Research-status Report
  • [Journal Article] Reliable imaging of ATP in living budding and fission yeast2019

    • Author(s)
      Takaine M, Ueno M, Kitamura K, Imamura H, Yoshida S.
    • Journal Title

      J Cell Sci.

      Volume: 132 Issue: 8 Pages: 1-11

    • DOI

      10.1242/jcs.230649

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Spindle pole body movement is affected by glucose and ammonium chloride in fission yeast2019

    • Author(s)
      Ito H, Sugawara T, Shinkai S, Mizukawa S, Kondo A, Senda H, Sawai K, Ito K, Suzuki S, Takaine M, Yoshida S, Imamura H, Kitamura K, Namba T, Tate SI, Ueno M
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 511 Issue: 4 Pages: 820-825

    • DOI

      10.1016/j.bbrc.2019.02.128

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell-based chemical fingerprinting identifies telomeres and lamin A as modifiers of DNA damage response in cancer cells2018

    • Author(s)
      Fujiwara C, Muramatsu Y, Nishii M, Tokunaka K, Tahara H, Ueno M, Yamori T, Sugimoto Y, Seimiya H8
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41598-018-33139-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutation in fission yeast phosphatidylinositol 4-kinase Pik1 is synthetically lethal with defect in telomere protection protein Pot12018

    • Author(s)
      Sugihara A, Nguyen LC, Shamim HM, Iida T, Nakase M, Takegawa K, Senda M, Jida S, Ueno M.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 496 Pages: 1284-1290

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chromosome passenger complex is required for the survival of cells with ring chromosomes in fission yeast2018

    • Author(s)
      Habib AGK, Sugiura K, Ueno M
    • Journal Title

      PLoS One

      Volume: 13 Issue: 1 Pages: 1-20

    • DOI

      10.1371/journal.pone.0190523

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fission yeast strains with circular chromosomes require the 9-1-1 checkpoint complex for the viability in response to the anti-cancer drug 5-fluorodeoxyuridine2017

    • Author(s)
      Shamim HM, Minami Y, Tanaka D, Ukimori S, Murray JM, Ueno M
    • Journal Title

      PLoS One

      Volume: 12 Issue: 11 Pages: 1-16

    • DOI

      10.1371/journal.pone.0187775

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Analysis of chromosome stability and dynamics in fission yeast2019

    • Author(s)
      上野 勝
    • Organizer
      The International Symposium on Biofunctional Chemistry
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Nucleolus dynamics is affected by different stresses and proteins that localize to nuclear membrane or telomere2019

    • Author(s)
      上野 勝
    • Organizer
      10th International Pombe 2019 meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of telomere-tethering protein for the regulation of nuclear organization and dynamics2019

    • Author(s)
      上野 勝
    • Organizer
      第42回日本分子生物学会年会ワークショップ
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 核構造や核動態の制御におけるテロメアテザリングタンパク質の役割2019

    • Author(s)
      上野 勝
    • 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] Spindle pole body movement is affected by glucose concentration, medium, and DNA replication stress in fission yeast2018

    • Author(s)
      Masaru Ueno
    • Organizer
      FASEB Yeast Chromosome Biology and Cell Cycle
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 染色体パッセンジャー複合体は環状染色体の維持に必要である2018

    • Author(s)
      上野 勝
    • Organizer
      日本農芸化学会2018年度名古屋大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 染色体パッセンジャー複合体は環状染色体の維持に必要である2017

    • Author(s)
      上野 勝
    • 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 Research-status Report
  • [Remarks] がん細胞に関連する環状染色体の維持に関わる新規因子を発見

    • URL

      https://www.hiroshima-u.ac.jp/adsm/news/43346

    • Related Report
      2017 Research-status Report

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

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