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Understanding the mechanisms by which Ctf4 protein promotes proper repair of DSBs formed upon inhibition of rDNA replication

Research Project

Project/Area Number 15K18581
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Genetics/Chromosome dynamics
Research InstitutionThe University of Tokyo

Principal Investigator

Sasaki Mariko  東京大学, 分子細胞生物学研究所, 助教 (50722013)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsDNA複製阻害 / DNA二重鎖切断 / Ctf4 / ゲノム再編成 / rDNA / ゲノム不安定化 / 複製阻害
Outline of Final Research Achievements

In this study, I aimed to understand the mechanisms by which Ctf4 protein functions to promote proper repair of DNA double-strand breaks (DSBs) at the arrested replication forks. It has been believed that DSBs at arrested forks are repaired by homologous recombination, which is required for repair of DSBs formed in the G2/M phases of the cell cycle. However, I found that DSBs at arrested forks are repaired by the novel pathways that are independent of homologous recombination. I also showed that Ctf4 protein, a component of replication machineries, plays an important role for proper repair of DSBs at arrested forks, by suppressing the initiation of homologous recombination upon DSB formation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (10 results)

All 2017 2016 2015

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

  • [Journal Article] Ctf4 Prevents Genome Rearrangements by Suppressing DNA Double-Strand Break Formation and Its End Resection at Arrested Replication Forks2017

    • Author(s)
      Sasaki Mariko、Kobayashi Takehiko
    • Journal Title

      Molecular Cell

      Volume: 66 Issue: 4 Pages: 533-545

    • DOI

      10.1016/j.molcel.2017.04.020

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] rDNA stability is supported by many "Buffer genes" -Introduction to the Yeast rDNA Stability Database.2017

    • Author(s)
      Kobayashi T, Sasaki M
    • Journal Title

      FEMS Yeast Res.

      Volume: - Issue: 1 Pages: 1-8

    • DOI

      10.1093/femsyr/fox001

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] レプリソームの構成タンパク質であるCtf4は複製が阻害された際に生じるDNA2本鎖切断の修復に重要である2017

    • Author(s)
      佐々木真理子、小林武彦
    • Journal Title

      First Author'sライフサイエンス新着論文レビュー

      Volume: ー

    • Related Report
      2017 Annual Research Report
  • [Journal Article] More than 10% of yeast genes are related to genome stability and influence cellular senescence via rDNA maintenance2016

    • Author(s)
      Kimiko Saka, Akihiro Takahashi, Mariko Sasaki and Takehiko Kobayashi
    • Journal Title

      Nucleic Acids Research

      Volume: in press Issue: 9 Pages: 1-11

    • DOI

      10.1093/nar/gkw110

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] DNA複製阻害時のDNA二重鎖切断修復機構の解明2017

    • Author(s)
      佐々木 真理子、小林 武彦
    • Organizer
      日本遺伝学会第89回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] A replisome component Ctf4 suppresses end resection of DNA double-strand breaks at the arrested forks to prevent chromosome rearrangements.2016

    • Author(s)
      Mariko Sasaki
    • Organizer
      The 10th 3R International Symposium.
    • Place of Presentation
      ホテル一畑(島根県松江市)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] DNA複製阻害によって生じるDNA二重鎖切断修復機構の解明2016

    • Author(s)
      佐々木 真理子
    • Organizer
      日本遺伝学会第88回大会
    • Place of Presentation
      日本大学国際関係学部(静岡県三島)
    • Year and Date
      2016-09-07
    • Related Report
      2016 Research-status Report
  • [Presentation] A replisome factor Ctf4 protects replication-associated DNA double-strand breaks from rearrangement-prone homologous recombination.2016

    • Author(s)
      Mariko Sasaki
    • Organizer
      Mechanisms of Recombination 2016
    • Place of Presentation
      アリカンテ(スペイン)
    • Year and Date
      2016-05-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 出芽酵母Ctf4による複製阻害に伴うDNA二重鎖切断形成及び修復制御2015

    • Author(s)
      佐々木 真理子
    • Organizer
      第23回 DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      焼津グランドホテル(静岡県焼津市)
    • Year and Date
      2015-10-19
    • Related Report
      2015 Research-status Report
  • [Presentation] Mechanism by which the Saccharomyces cerevisiae Ctf4 protein prevents rDNA hyper-amplification2015

    • Author(s)
      Mariko Sasaki
    • Organizer
      2015 FASEB Science Research Conferences Genetic Recombination & Genome Rearrangements
    • Place of Presentation
      Steamboat Springs, Colorado, USA
    • Year and Date
      2015-07-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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