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Roles of replication stress for cellular senescence and genome instability in preneoplastic lesions

Research Project

Project/Area Number 23501257
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Carcinogenesis
Research InstitutionGunma University

Principal Investigator

YAMASHITA Takayuki  群馬大学, 生体調節研究所, 教授 (10166671)

Co-Investigator(Kenkyū-buntansha) ODA Tsukasa  群馬大学, 生体調節研究所, 助教 (10323643)
SEKIMOTO Takayuki  群馬大学, 生体調節研究所, 助教 (20436322)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsDNA複製 / DNA複製ストレス / Y-family polymerase / cyclin E / geminin / ゲノム不安定性 / 前がん病変 / 発がん / Yファミリー・ポリメラーゼ / 発がん遺伝子 / 突然変異 / ゲノム不安定化
Research Abstract

In preneoplastic lesions, oncogene-induced replication stress plays a dual role induction of cell senescence/apoptosis and tumor promotion through increased genomic instability. In these processes, oncogene-induced excessive activation of replication origins and consequent rereplication plays a major role. However, little is known about fork progression during rereplication. When rereplication was induced by depletion of geminin, a regulator of origin activation, Pol-eta was recruited to rereplication sites in human cell lines. Similar observations were obtained in cyclin E-induced rereplication in human tumor cells. Furthermore, Pol-eta knockdown suppressed rereplication induced by either geminin depletion or cyclin E expression. Together, our data suggest that Pol-eta participates in oncogene-induced rereplication. These findings provide important mechanistic insights into genomic instability during tumorigenesis.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (30 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results) Presentation (20 results) Remarks (3 results)

  • [Journal Article] Matched sibling donor stem cell transplantation for Fanconi anemia patients with T-cell somatic mosaicism2012

    • Author(s)
      Yabe M, Shimizu T, Morimoto T, Koike T, Takakura H, Tsukamoto H, Muroi K, Oshima K, Asami K, Takata M, Yamashita T, Kato S, Yabe H
    • Journal Title

      Pediatric Transplant

      Volume: (印刷中) Issue: 4 Pages: 340-345

    • DOI

      10.1111/j.1399-3046.2012.01669.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Translesion DNA synthesis and hsp902012

    • Author(s)
      Yamashita T, Oda T, Sekimoto T
    • Journal Title

      Genes and Environment

      Volume: 34 Pages: 89-93

    • NAID

      10030311653

    • URL

      https://www.jstage.jst.go.jp/article/jemsge/34/2/34_GE-2012-0006/_article

    • Related Report
      2013 Final Research Report
  • [Journal Article] Translesion DNA synthesis and Hsp902012

    • Author(s)
      Takayuki Yamashita
    • Journal Title

      Genes and Environment

      Volume: 34 Pages: 89-93

    • NAID

      10030311653

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct Inhibition of TNF-α Promoter Activity by Fanconi Anemia Prote in FANCD22011

    • Author(s)
      Nobuko Matsushita, Yujiro Endo, Koichi Sato, Hitoshi Kurumizaka, Takayuki Yamashita, Minoru Takata, Shigeru Yanagi
    • Journal Title

      PLoS One

      Volume: 6(電子媒体による発表) Issue: 8 Pages: e23324-e23324

    • DOI

      10.1371/journal.pone.0023324

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL112011

    • Author(s)
      Sasaki M, Kawahara K, Nishio M, Mimori K, Kogo R, Hamada K, Itoh B, Wang J, Komatsu Y, Yang YR, Hikasa H, Horie Y, Yamashita T, Kamijo T, Zhang Y, Zhu Y, Prives C, Nakano T, Mak TW, Sasaki T, Maehama T, Mori M, Suzuki A
    • Journal Title

      Nat Med

      Volume: 17 Issue: 8 Pages: 944-951

    • DOI

      10.1038/nm.2392

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular chaperone Hsp90 regulates REV1-mediated mutagenesis2011

    • Author(s)
      Pozo FM, Oda T, Sekimoto T, Murakumo Y, Masutani C, Hanaoka F, Yamashita T
    • Journal Title

      Mol Cell Biol

      Volume: 31 Pages: 3396-3409

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular chaperone Hsp90 regulates REV1-mediated mutagenesis.2011

    • Author(s)
      Pozo FM
    • Journal Title

      Mol Cell Biol

      Volume: 31 Issue: 16 Pages: 3396-3409

    • DOI

      10.1128/mcb.05117-11

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] DNA polymerase-eta promotes DNA rereplication2014

    • Author(s)
      山下孝之
    • Organizer
      International symposium on xeroderma pigmentosum and related disorders
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] DNA polymerase η promotes DNA rereplication2014

    • Author(s)
      山下孝之
    • Organizer
      International symposium on xeroderma pigmentosum and related disorders
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research 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可能性がある2013

    • Author(s)
      小田 司、関本隆志、山下孝之
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] Polymerase-eta は発がん遺伝子が誘導するDNA 再複製に関与する2013

    • Author(s)
      関本隆志、小田司、花岡文雄、山下孝之
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research 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2013

    • Author(s)
      関本隆志、小田司、益谷央豪、花岡文雄、山下孝之
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research 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、小田司、益谷央豪、花岡文雄、山下孝之
    • Organizer
      第72回日本癌学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research 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、関本隆志、山下孝之
    • Organizer
      第72回日本癌学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Polymerase η は発がん遺伝子が誘導するDNA再複製に関与する2013

    • Author(s)
      関本隆志、小田司、益谷央豪、山下孝之
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research 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、関本隆志、山下孝之
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research 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、小田司、益谷央豪、花岡文雄、山下孝之
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 熱ショック応答転写因子Heat shock factor 1 (HSF1)の抑制によるp53 依存性細胞老化にはDHRS2 の発現誘導が重要である2012

    • Author(s)
      小田 司、関本隆志、山下孝之
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Polymerase-eta is involved in oncogene-induced DNA re-replication and DNA damage responses2012

    • Author(s)
      関本隆志、小田司、益谷央豪、花岡文雄、山下孝之
    • Organizer
      第71回 日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Polymerase-eta is involved in oncogene-induced DNA re-replication and DNA damage responses2012

    • Author(s)
      関本隆志
    • Organizer
      第71回 日本癌学会学術総会
    • Place of Presentation
      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 日本分子生物学会年会
    • Place of Presentation
      福岡
    • 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p53依存性細胞老化にはDHRS2の発現誘導が重要である2012

    • Author(s)
      小田 司
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 熱ショック応答転写因子Heat shock factor 1 (HSF1)の転写活性の抑制はp53-p21 経路を介した細胞老化を誘導する2011

    • Author(s)
      小田 司、関本隆志、山下孝之
    • Organizer
      第34回 日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Y-family DNA ポリメラーゼによる損傷乗り越えDNA 合成は、cyclin E過剰発現によるDNA 複製ストレス応答に関与する2011

    • Author(s)
      関本隆志、小田司、益谷央豪、花岡文雄、山下孝之
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 分子シャペロンHsp90 はREV1 による突然変異の誘発を制御する2011

    • Author(s)
      マイカ ポゾ フランクリン、小田司、関本隆志、村雲芳樹、益谷央豪、花岡文雄、山下孝之
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 熱ショック転写因子HSF1 の急性欠乏は複数の腫瘍抑制経路を介して細胞老化プログラムを活性化する2010

    • Author(s)
      小田司、関本隆志、山下孝之
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] Y-family DNAポリメラーゼによる損傷乗り越えDNA合成は、cyclin E過剰発現によるDNA複製ストレス応答に関与する

    • Author(s)
      関本隆志、山下孝之ら
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Remarks] ホームページ等

    • URL

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

    • Related Report
      2013 Final 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 Annual Research 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: 2011-08-05   Modified: 2019-07-29  

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