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The mechanism of chromosome instability in telomere crisis

Research Project

Project/Area Number 16H06176
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Genetics/Chromosome dynamics
Research InstitutionKyoto University

Principal Investigator

Hayashi Makoto  京都大学, 白眉センター, 特定助教 (90761099)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥22,490,000 (Direct Cost: ¥17,300,000、Indirect Cost: ¥5,190,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywordsテロメアクライシス / テロメア脱保護 / M期停止 / 細胞周期 / BLM / TRF1 / M期 / CRISPR/Cas9 / がん / 染色体 / クライシス / テロメア / 染色体融合
Outline of Final Research Achievements

By using artificial DNA sequences, we constructed a unique system that is capable of labeling cells with a single sister chromatid fusion. We analyzed the fate of sister chromatid fusion using this system. We found that a single sister chromatid fusion is enough to induce chromosome aberrations such as micronuclei and chromosome scattering. Besides, we attempted to elucidate the molecular mechanism of mitotic telomere deprotection, which we originally discovered. We have successfully identified factors such as telomere binding protein TRF1 and DNA helicase BLM as factors involved in this phenomenon. Also, we found that the combination of TRF1 and BLM contributed to this phenomenon.

Academic Significance and Societal Importance of the Research Achievements

染色体の融合は、細胞のガン化と密接に関わっているが、染色体融合の種類、数、時期などを明確に制御する系が存在しなかったため、染色体融合の運命については複数の仮説が存在していた。本研究成果により、単一の姉妹染色分体融合の運命が解析可能となり、細胞ガン化のメカニズムの理解に貢献することが期待される。また、M期停止はある種の抗がん剤によって引き起こされるため、M期停止中のテロメア脱保護の分子機構の解析によって、抗がん剤の副作用の軽減や、効果的な併用療法などの開発が展望できる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (36 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 3 results) Presentation (27 results) (of which Int'l Joint Research: 13 results,  Invited: 10 results)

  • [Int'l Joint Research] Children's Medical Research Institute(オーストラリア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Children's Medical Research Institute(オーストラリア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Children’s Medical Research Institute(オーストラリア)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Replication stress induces mitotic death through parallel pathways regulated by WAPL and telomere deprotection2019

    • Author(s)
      Masamsetti V. Pragathi、Low Ronnie Ren Jie、Mak Ka Sin、O’Connor Aisling、Riffkin Chris D.、Lamm Noa、Crabbe Laure、Karlseder Jan、Huang David C. S.、Hayashi Makoto T.、Cesare Anthony J.
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41467-019-12255-w

    • NAID

      120006726158

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A single defined sister chromatid fusion destabilizes cell cycle through micronuclei formation2019

    • Author(s)
      Katsushi Kagaya, Naoto Noma, Io Yamamoto, Sanki Tashiro, Fuyuki Ishikawa, Makoto T Hayashi
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/607341

    • Related Report
      2019 Annual Research Report
    • Open Access
  • [Journal Article] テロメアの生物学―老化・がん化の分子基盤2018

    • Author(s)
      林 眞理
    • Journal Title

      実験医学 増刊 染色体の新常識

      Volume: 36 Pages: 44-51

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Telomere biology in aging and cancer: early history and perspectives.2017

    • Author(s)
      Makoto T Hayashi
    • Journal Title

      Genes & Genetic Systems

      Volume: 92 Pages: 107-118

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanism of mitotic cell death during telomere crisis2016

    • Author(s)
      林 眞理
    • Journal Title

      生化学

      Volume: 88 Issue: 6 Pages: 756-760

    • DOI

      10.14952/SEIKAGAKU.2016.880756

    • NAID

      40021054367

    • ISSN
      0037-1017
    • Year and Date
      2016-12-25
    • Related Report
      2016 Annual Research Report
  • [Journal Article] テロメア・テロメレースによる老化制御2016

    • Author(s)
      林眞理
    • Journal Title

      日本臨牀 老化制御と疾患-エイジング研究の進歩-

      Volume: 74(9) Pages: 1485-1490

    • Related Report
      2016 Annual Research Report
  • [Presentation] A Single Defined Sister Chromatid Fusion Destabilizes Cell Cycle through Micronuclei Formation2019

    • Author(s)
      Makoto T Hayashi
    • Organizer
      The 78th Annual Meeting of the Japanese Caner Association
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Single Defined Sister Chromatid Fusion Destabilizes Cell Cycle through Micronuclei Formation Cold Spring Harbor Meeting Telomeres & Telomerase2019

    • Author(s)
      Makoto T Hayashi
    • Organizer
      Cold Spring Harbor Meeting Telomeres & Telomerase
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A Single Defined Sister Chromatid Fusion Destabilizes Cell Cycle through Micronuclei Formation2019

    • Author(s)
      Makoto T Hayashi
    • Organizer
      ACCM2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 染色体融合可視化システムによる姉妹染色分体融合の運命解析2019

    • Author(s)
      林眞理
    • Organizer
      第71回細胞生物学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 単一の姉妹染色分体融合によるゲノム不安定化メカニズム2019

    • Author(s)
      林眞理
    • Organizer
      国立遺伝学研究所研究会「染色体安定維持研究会」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Sister Chromatid Fusion Visualization System Revealed Micronuclei Formation as an Initial Event2019

    • Author(s)
      Makoto T Hayashi
    • Organizer
      The 8th Meeting on GRANT-IN-AID FOR SCIENTIFIC RESEARCH ON INNOVATIVE AREAS “CHROMOSOME ORCHESTRATION SYSTEM"
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 姉妹染色分体可視化システムを用いた融合運命のベイズ解析2019

    • Author(s)
      林 眞理
    • Organizer
      Genome Damage Network Workshop 2019
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 姉妹染色分体可視化システムを用いた融合運命のベイズ解析2019

    • Author(s)
      林 眞理
    • 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] 染色体融合可視化システムによる姉妹染色分体融合の運命解析2019

    • Author(s)
      林 眞理
    • Organizer
      第36回染色体ワークショップ、第17回核ダイナミクス研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Epithelial-to-mesenchymal transition dictates cellular fate upon chromosome fusion2018

    • Author(s)
      Makoto T Hayashi
    • Organizer
      CEBST2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epithelial-mesenchymal state dictates cellular fate upon chromosome fusion2018

    • Author(s)
      Makoto T Hayashi
    • Organizer
      The 7th Meeting on GRANT-IN-AID FOR SCIENTIFIC RESEARCH ON INNOVATIVE AREAS “CHROMOSOME ORCHESTRATION SYSTEM”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genetically Encoded Tool for Visualization of Sister Chromatid Fusion Revealed Micronuclei Formation as an Initial Event2018

    • Author(s)
      Makoto T Hayashi
    • Organizer
      3R & 3C meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chromosome fusion delays S/G2 phase prior to mitotic arrest in human fibroblast cells2018

    • Author(s)
      Makoto T Hayashi
    • Organizer
      EMBO Workshop Telomere biology in health and human disease
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 染色体融合の運命解析2018

    • Author(s)
      林 眞理
    • Organizer
      新学術領域研究「染色体オーケストレーションシステム」第5回領域班会議
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fate of sister chromatid fusion by fusion-visualization-system2017

    • Author(s)
      Makoto Hayashi
    • Organizer
      The 4th Meeting on GRANT-IN-AID FOR SCIENTIFIC RESEARCH ON INNOVATIVE AREAS “CHROMOSOME ORCHESTRATION SYSTEM”
    • Place of Presentation
      The Royal Society London
    • Year and Date
      2017-02-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 染色体融合可視化システムによる姉妹染色体分体融合の運命解析2017

    • Author(s)
      林眞理
    • Organizer
      ワークショップ染色体研究の最前線
    • Place of Presentation
      大阪大学生命機能研究科
    • Year and Date
      2017-01-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 染色体融合可視化システムによる姉妹染色分体融合の運命解析2017

    • Author(s)
      林眞理
    • 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
      かずさアカデミアホール
    • Year and Date
      2017-01-11
    • Related Report
      2016 Annual Research Report
  • [Presentation] Can aging be controlled?2017

    • Author(s)
      Makoto Hayashi
    • Organizer
      Japanese-Canadian Frontiers of Science Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 染色体融合可視化システムによる姉妹染色分体融合の運命解析2017

    • Author(s)
      林 眞理
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] がん化初期過程であるテロメアクライシスにおける細胞死機構の解明2017

    • Author(s)
      林 眞理
    • Organizer
      第10回Symphony
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 染色体融合可視化システムによる姉妹染色体分体融合の運命解析2017

    • Author(s)
      林 眞理
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 異なる細胞種における染色体融合の運命解析2017

    • Author(s)
      林 眞理
    • 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] 染色体融合可視化システムによる姉妹染色体分体融合の運命解析2017

    • Author(s)
      林 眞理
    • Organizer
      染色体構築と安定化を担う分子機構
    • Related Report
      2017 Annual Research Report
  • [Presentation] 染色体融合の運命解析2017

    • Author(s)
      林 眞理
    • Organizer
      新学術領域研究「染色体オーケストレーションシステム」第6回領域班会議
    • Related Report
      2017 Annual Research Report
  • [Presentation] The Fate of Chromosome Fusion during Telomere Crisis2016

    • Author(s)
      Makoto T hayashi, Anthony J Cesare and Jan Karlseder
    • Organizer
      The 75th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Pacifico Yokohama
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell Death During Crisis Is Mediated by Mitotic Telomere Deprotection2016

    • Author(s)
      Makoto T hayashi, Anthony J Cesare and Jan Karlseder
    • Organizer
      The 32th RBC International Symposium
    • Place of Presentation
      Coop Inn Kyoto
    • Year and Date
      2016-09-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 染色体融合運命の継時的理解を目指して2016

    • Author(s)
      林眞理
    • Organizer
      新学術領域研究「染色体オーケストレーションシステム」第3回領域班会議
    • Place of Presentation
      山形瀧波旅館
    • Year and Date
      2016-07-19
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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