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Defining the molecular mechanism of the cell cycle-specific regulation of chromosome end fusion at dysfunctional telomeres

Research Project

Project/Area Number 25440080
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cell biology
Research InstitutionGunma University

Principal Investigator

Konishi Akimitsu  群馬大学, 大学院医学系研究科, 講師 (50381877)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsテロメア / 染色体不安定化 / DNA損傷反応 / DNA修復 / 細胞周期 / 染色体末端融合 / 細胞癌化 / クロマチン
Outline of Final Research Achievements

In this study, we aimed to elucidate the molecular mechanism of the cell cycle-specific regulation of chromosome end fusion leading to the cell carcinogenesis. We revealed that chromatin ubiquitination at the end of chromosomes induced by telomere dysfunction was largely diminished in S/G2 cell cycle phase. As a result, the recruitment of 53BP1, which is an essential factor for chromosome end fusion, is suppressed in S/G2 phase. We also elucidated that TRF2, the central factor for telomere protection, directly binds to the chromatin (core histone) to stabilize the chromosome ends.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (27 results)

All 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Int'l Joint Research: 4 results) Remarks (5 results)

  • [Int'l Joint Research] The Rockefeller University(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] The Scripps Research Institute(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] TRF2 Protein Interacts with Core Histones to Stabilize Chromosome Ends.2016

    • Author(s)
      Konishi A, Izumi T, Shimizu S
    • Journal Title

      J Biol Chem.

      Volume: 291(39) Issue: 39 Pages: 20798-810

    • DOI

      10.1074/jbc.m116.719021

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autophagy controls centrosome number by degrading Cep63.2016

    • Author(s)
      Watanabe Y, Honda S, Konishi A, Satoko Arakawa S, Murohashi M, Yamaguchi H, Torii S, Tanabe M, Tanaka S, Warabi E, Shimizu S.
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 13508-13508

    • DOI

      10.1038/ncomms13508

    • NAID

      120007129257

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enzymatic characterization of recombinant rat DDHD2: a soluble diacylglycerol lipase.2016

    • Author(s)
      Araki M, Ohshima N, Aso C, Konishi A, Obinata H, Tatei K, Izumi T.
    • Journal Title

      J. Biochem.

      Volume: 160 Issue: 5 Pages: 269-279

    • DOI

      10.1093/jb/mvw034

    • NAID

      40021012775

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Protein purification and cloning of diacylglycerol lipase from rat brain.2016

    • Author(s)
      Aso C, Araki M, Ohshima N, Tatei K, Hirano T, Obinata H, Kishi M, Kishimoto K, Konishi A, Goto F, Sugimoto H, Izumi T.
    • Journal Title

      J. Biochem.

      Volume: 159 Issue: 6 Pages: 585-597

    • DOI

      10.1093/jb/mvw002

    • NAID

      40020869378

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] TRF2はコアヒストンとの直接結合によりテロメアのループ構造を維持する2017

    • Author(s)
      小西 昭充、和泉 孝志、清水 重臣
    • Organizer
      第34回染色体ワークショップ
    • Place of Presentation
      松島
    • Year and Date
      2017-01-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] オートファジーによるCep63の分解を介した中心体数の制御2016

    • Author(s)
      本田 真也, 渡辺 雄一郎, 小西 昭充, 室橋 道子, 荒川 聡子, 山口 啓史, 清水 重臣
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Cell cycle-dependent regulation of DNA damage response at dysfunctional telomeres2016

    • Author(s)
      Hiraku Suzuki, Anastasie Tshilela Kadiombo, Akimitsu Konishi, Takashi Izumi
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Cell Cycle-Dependent Regulation of DNA Damage Response and DNA Repair at Dysfunctional Telomeres2016

    • Author(s)
      Akimitsu Konishi
    • Organizer
      10th 3R Symposium
    • Place of Presentation
      Matsue
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] テロメアにおける細胞周期依存的なDNA損傷反応・DNA修復の制御機構2016

    • Author(s)
      小西 昭充
    • Organizer
      第6回DNA損傷応答ワークショップ
    • Place of Presentation
      浜松
    • Year and Date
      2016-04-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] Cell cycle-dependent regulation of non-homologous end joining at unprotected telomeres2016

    • Author(s)
      Kadiombo Tshilela Anastasie, Akimitsu Konishi, Takashi Izumi
    • Organizer
      第33回染色体ワークショップ
    • Place of Presentation
      松島一の坊(宮城県宮城郡松島町)
    • Year and Date
      2016-01-12
    • Related Report
      2015 Research-status Report
  • [Presentation] TRF2 interacts with core histones to stabilize chromosome ends2015

    • Author(s)
      Akimitsu Konishi
    • Organizer
      EMBO Workshop Telomeric Chromatin and telomere fragility
    • Place of Presentation
      Singapore(シンガポール)
    • Year and Date
      2015-12-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Complete sequence of human telomere DNA by single-molecule real-time sequencing technique2015

    • Author(s)
      Kaori Yauchi, Akimitsu Konishi, Takashi Izumi
    • Organizer
      EMBO Workshop Telomeric Chromatin and telomere fragility
    • Place of Presentation
      Singapore(シンガポール)
    • Year and Date
      2015-12-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cell cycle-dependent regulation of non-homologous end joining at unprotected telomeres2015

    • Author(s)
      Kadiombo Tshilela Anastasie, Akimitsu Konishi, Takashi Izumi
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Cell Cycle-Dependent Regulation of DNA Damage Response and DNA Repair at Dysfunctional Telomeres2015

    • Author(s)
      Akimitsu Konishi
    • Organizer
      Cold Spring Harbor Meeting Telomere & Telomerase
    • Place of Presentation
      Cold Spring Harbor, NY (米国)
    • Year and Date
      2015-04-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cell Cycle-Dependent Regulation of DNA Damage Response and DNA Repair at Dysfunctional Telomeres.2014

    • Author(s)
      Akimitsu Konishi, Takashi Izumi, Titia de Lange
    • Organizer
      4D Nucleome
    • Place of Presentation
      広島
    • Year and Date
      2014-12-17 – 2014-12-20
    • Related Report
      2014 Research-status Report
  • [Presentation] テロメアにおける細胞周期依存的なDNA損傷反応・DNA修復の制御機構2014

    • Author(s)
      小西昭充、和泉孝志、Titia de Lange
    • Organizer
      染色体ワークショップ
    • Place of Presentation
      広島
    • Year and Date
      2014-12-15 – 2014-12-17
    • Related Report
      2014 Research-status Report
  • [Presentation] テロメアでの細胞周期依存的なDNA損傷反応・DNA修復の制御機構2014

    • Author(s)
      小西昭充、和泉孝志、Titia de Lange
    • Organizer
      第37回分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Wee1 によるDNA損傷チェックポイントの回復制御2013

    • Author(s)
      小西昭充、和泉孝志、清水重臣
    • Organizer
      第31回染色体ワークショップ
    • Place of Presentation
      箱根
    • Related Report
      2013 Research-status Report
  • [Presentation] Regulation of DNA damage checkpoint termination2013

    • Author(s)
      Akimitsu Konishi, Takashi Izumi, Shigeomi Shimizu
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] 細胞はどのようにしてDNA損傷から回復するのか

    • Author(s)
      小西昭充
    • Organizer
      群馬大学ASRLDシンポジウム
    • Place of Presentation
      前橋
    • Related Report
      2013 Research-status Report
  • [Remarks] 群馬大学大学院医学系研究科・代謝機能制御系器官機能制御学・生化学

    • URL

      http://www.med.gunma-u.ac.jp/med-organization/bioreg/bioreg-function/123.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 群馬大学大学院医学系研究科・テニュアトラック普及推進室

    • URL

      http://tenure.showa.gunma-u.ac.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 群馬大学大学院医学系研究科テニュアトラック普及推進室

    • URL

      http://tenure.showa.gunma-u.ac.jp

    • Related Report
      2015 Research-status Report 2014 Research-status Report
  • [Remarks] 群馬大学大学院医学系研究科生化学教室

    • URL

      http://biochemistry.dept.med.gunma-u.ac.jp

    • Related Report
      2013 Research-status Report
  • [Remarks] 群馬大学大学院医学系研究科テニュアトラック普及推進室

    • URL

      http://tenure.showa.gunma-u.ac.jp

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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