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Analysis of replication stress responses caused by oncogenic signals

Research Project

Project/Area Number 24700952
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Carcinogenesis
Research InstitutionGunma University

Principal Investigator

SEKIMOTO Takayuki  群馬大学, 生体調節研究所, 助教 (20436322)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords複製ストレス / Y-familyポリメラーゼ / 発がん遺伝子 / 発がん / DNA再複製 / がん遺伝子
Outline of Final Research Achievements

DNA rereplication is a major type of oncogene-induced aberrant replication and plays an important role in genomic instability during tumor development. Rereplication causes DNA double strand breaks, resulting in copy number changes and genomic rearrangements. However, little is known on what DNA polymerases are involved in rereplication. Normal DNA replication is catalyzed by high-fidelity replicative polymerases, Pol ε and Pol δ. Y-family polymerases (Y-Pols) are the major group of low-fidelity polymerases whose main function is bypass of replication blocks at sites of DNA damages, i.e. translesion synthesis. We found that Y-Pols as well as replicative polymerases, participate in rereplication.
The present findings have important mechanistic implications in genomic instability during tumorigenesis. Speculatively, the involvement of Y-Pols in rereplication may account for frequent occurrence of single nucleotide variations in conjunction with gene rearrangements in cancer genomes.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (16 results)

All 2015 2014 2013 2012 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) Remarks (4 results)

  • [Journal Article] Both high-fidelity replicative and low-fidelity Y-family polymerases are involved in DNA rereplication.2015

    • Author(s)
      Sekimoto T, Oda T, Kurashima K, Hanaoka F, Yamashita T
    • Journal Title

      Mol Cell Biol

      Volume: 35 Issue: 4 Pages: 699-715

    • DOI

      10.1128/mcb.01153-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] DNA polymerase η (Polη) suppresses c-myc-induced replication stress2014

    • Author(s)
      倉島公憲、小田司、関本隆志、花岡文雄、山下孝之
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Inhibition of Heat Shock Factor 1 (HSF1) selectively activates cellular senescence program in Ras V12-transformed cells2014

    • Author(s)
      小田司、関本隆志、倉島公憲、山下孝之
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ポリメラーゼηはがん遺伝子が誘導するDNA再複製に関与する2014

    • Author(s)
      関本隆志
    • Organizer
      がん支援活動冬期公開シンポジウム
    • Place of Presentation
      学術総合センター一橋講堂
    • Related Report
      2013 Research-status Report
  • [Presentation] Y-familyポリメラーゼは発がんシグナルが誘導するDNA再複製に関与する2013

    • Author(s)
      関本隆志
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] DHRS2は熱ショック転写因子HSF1抑制で誘導される細胞老化に関与する2013

    • Author(s)
      小田司
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] ポリメラーゼηは発がんシグナルが誘導するDNA再複製に関与する2013

    • Author(s)
      関本隆志
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Research-status Report
  • [Presentation] DHRS2は、熱ショック転写因子HSF1の発現抑制で誘導される細胞老化に関与する可能性がある2013

    • Author(s)
      小田司
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Research-status Report
  • [Presentation] c-MycによるDNA複製ストレスにDNAポリメラーゼηが関与する2013

    • Author(s)
      倉島公憲
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Research-status Report
  • [Presentation] ポリメラーゼηは発がんシグナルが誘導するDNA再複製とDNA損傷応答に関与する2012

    • Author(s)
      関本隆志
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Y-family DNAポリメラーゼは、発がんシグナルが誘導するDNA再複製に関与する2012

    • Author(s)
      関本隆志
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] 熱ショック応答転写因子Heat shock factor 1 (HSF1)の抑制による細胞老化の誘導機構:DHRS2とp300/CBPの関与2012

    • Author(s)
      小田司
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2012 Research-status Report
  • [Remarks] 群馬大学生体調節研究所

    • URL

      http://www.imcr.gunma-u.ac.jp

    • Related Report
      2014 Annual Research Report
  • [Remarks] 群馬大学生体調節研究所遺伝子情報分野

    • URL

      http://molgen.imcr.gunma-u.ac.jp

    • Related Report
      2014 Annual Research Report
  • [Remarks] 群馬大学生体調節研究所遺伝子情報分野

    • URL

      http://molgen.imcr.gunma-u.ac.jp

    • Related Report
      2013 Research-status Report
  • [Remarks] 群馬大学生体調節研究所遺伝子情報分野

    • URL

      http://www.imcr.gunma-u.ac.jp/lab/molgen/

    • Related Report
      2012 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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