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Analysis of the mechanisms that prevent rereplication-induced genome instability

Research Project

Project/Area Number 15H06638
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionToho University

Principal Investigator

TSUYAMA Takashi  東邦大学, 薬学部, 助教 (70436096)

Project Period (FY) 2015-08-28 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsDNA複製 / 再複製 / Cdt1 / ゲノム安定性維持 / 複製フォーク / ゲノム安定性維持機構 / 遺伝子 / 癌 / ゲノム / 蛋白質 / 老化 / アフリカツメガエル卵抽出液
Outline of Final Research Achievements

Deregulation of DNA replication causes rereplication, which is involved in the genome instability. We have found that Cdt1 contributes to the maintenance of genome stability by suppressing DNA synthesis. In this study, we aimed to identify the pathway that prevents rereplication-induced genome instability, and to elucidate the mechanisms of replication inhibition by Cdt1. We found that 1) Cdt1 inhibits nascent strand elongation by suppressing the progression of replication forks, 2) amino acids 255-289 have a crucial role in Cdt1’s inhibitory activity, and 3) Cdt1’s licensing activity is not essential for replication inhibition.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • Research Products

    (5 results)

All 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results)

  • [Journal Article] Excess Cdt1 inhibits nascent strand elongation by repressing the progression of replication forks in Xenopus egg extracts.2016

    • Author(s)
      Nakazaki Y, Tsuyama T, Seki M, Takahashi M, Enomoto T, Tada S.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 470 Issue: 2 Pages: 405-410

    • DOI

      10.1016/j.bbrc.2016.01.028

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] DNA複製阻害タンパク質Gemininの構造と機能に関する解析2017

    • Author(s)
      後藤 勇貴、井堀 康太、山内 直之、森 洋介、中崎 祐太、津山 崇、東 祐太郎、多田 周右
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] アフリカツメガエル卵抽出液を用いたDNA複製におけるCdt1の新生鎖伸長抑制作用のメカニズムの解析2016

    • Author(s)
      中崎 祐太、津山 崇、東 祐太郎、高橋 美樹子、多田 周右
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] DNA複製ライセンス化機構におけるタンパク質間相互作用の生化学的解析2016

    • Author(s)
      津山 崇、中崎 祐太、東 祐太郎、多田 周右
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] 新生鎖伸長反応の抑制に関与するCdt1の機能領域とその作用機序に関する検討2016

    • Author(s)
      中崎 祐太、津山 崇、東 祐太郎、高橋 美樹子、多田 周右
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-29
    • Related Report
      2015 Annual Research Report

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Published: 2015-08-26   Modified: 2018-03-22  

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