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Studies on interfaces between DNA replication and DNA damage responses through multiple clamp and clamp loader proteins

Research Project

Project/Area Number 14380328
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionKYUSHU UNIVERSITY (2003-2004)
Nara Institute of Science and Technology (2002)

Principal Investigator

TSURIMOTO Toshiki  Kyushu University, Faculty of Sciences Department of Biology, Professor, 大学院・理学研究院, 教授 (30163885)

Co-Investigator(Kenkyū-buntansha) SHIOMI Yasushi  Kyushu University, Faculty of Sciences, Department of Biology, Postdoc, 大学院・理学研究院, 学術研究員 (80380567)
小布施 力史  奈良先端科学技術大学院大学, バイオサイエンス研究科, 助手 (00273855)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2004: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2002: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsChromosome cohesion / DNA nolymerase / ATPase / Mass spectrometry / Clamp / Clamp loader / DNA elongation / Check point / ユビキチン / 蛋白質イメージング / PCNA結合因子 / バキュロウイルス発現系 / DNAヘリカーゼ
Research Abstract

DNA elongation reaction during eukaryotic DNA replication requires a set of replication proteins, PCNA and RFC, which function as a clamp and its loader protein, respectively. So far, their related proteins have been identified, for example, Rad9-1-1,rad17,Chl12,Mgs1, and expected to function as a novel clamp and loader proteins. Due to their similarities with PCNA and RFC, they will have central roles as connectors of various DNA metabolic pathways originated from DNA replication. To elucidate a whole feature of this network of multiple clamp and clamp loader proteins to maintain genome stability during DNA replication, we have studied on their structures and functions.
First, we have reconstituted a novel clamp complex (9-1-1) and a loader complex (Rad17-RFC), both of which are required for the human checkpoint pathway. We further demonstrated that they have indistinguishable structures from those of PCNA and RFC, respectively. Thus, a specific clamp and loader proteins will have a particular role in the checkpoint response pathway. Second, we have reconstituted a loader complex with chromosome cohesion factor, Chl12, and demonstrated that this complex functions as the second PCNA loader. Third, we purified one of RFC-related proteins, WRNIP1, which has been identified as a Werner DNA helicase binding protein. This protein forms a self-oligomerized complex and exhibits ATPase activity. Furthermore, since it interacts specifically with DNA polymerase δ and stimulates the activity, it will be involved in regulation of DNA synthesis during DNA replication.
These results strongly suggest that multiple PCNA- and RFC-related proteins would organize a huge protein network to coordinate DNA replication and various pathways for precise DNA replication and chromosome segregation.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (35 results)

All 2005 2004 2003 2002 Other

All Journal Article (20 results) Book (6 results) Publications (9 results)

  • [Journal Article] Human Werner helicase interacting protein 1 (WRNIP1) functions as a novel modulator for DNA polymerase δ.2005

    • Author(s)
      T.Tsurimoto
    • Journal Title

      Genes to Cells 10

      Pages: 13-22

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human Werner helicase interacting protein 1 (WRNIP1) functions as a novel modulator for DNA polymerase δ2005

    • Author(s)
      Tsurimoto, T., Shinozaki, A., Yano, M., Seki, M., Enomoto, T.
    • Journal Title

      Genes Cells. 10

      Pages: 13-22

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human Werner helicase interacting protein I(WRNIP1) functions as a novel modulator for DNA polymerase δ.2005

    • Author(s)
      T.Tsurimoto
    • Journal Title

      Genes to Cells 10

      Pages: 13-22

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination2004

    • Author(s)
      K.Watanabe
    • Journal Title

      EMBO J. 23

      Pages: 3886-3896

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The reconstituted human Chl12-RFC complex functions as a second PCNA loader.2004

    • Author(s)
      Y.Shiomi
    • Journal Title

      Genes to Cells 9

      Pages: 279-290

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination.2004

    • Author(s)
      Kawasuji, M., Tsurimoto, T., Inoue, H., Yamaizumi M.
    • Journal Title

      EMBO J. 23

      Pages: 3886-3896

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The reconstituted human Chl12-RFC complex functions as a second PCNA loader.2004

    • Author(s)
      Shiomi Y, Shinozaki A.Sugimoto K, Usukura J, Obuse, C, Tsurimoto T.
    • Journal Title

      Genes Cells. 9

      Pages: 279-290

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination2004

    • Author(s)
      K.Watanbe
    • Journal Title

      EMBO J. 23

      Pages: 3886-3896

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The ORC1 cycle in human cells : I. Cell cycle-regulated oscillation of human ORC1.2003

    • Author(s)
      Y.Tatsumi
    • Journal Title

      J.Biol.Chem. 278

      Pages: 41528-41534

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The ORC1 cycle in human cells : II. Dynamic changes in the human ORC complex during the cell cycle.2003

    • Author(s)
      S.Ohta
    • Journal Title

      J.Biol.Chem. 278

      Pages: 41535-41540

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The ORC1 cycle in human cells : I. Cell cycle-regulated oscillation of human ORC1.2003

    • Author(s)
      Tatsumi, Y., Ohta, S., Kimura, H., Tsurimoto, T., Obuse, C.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 41528-41534

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The ORC1 cycle in human cells : II. Dynamic changes in the human ORC complex during the cell cycle.2003

    • Author(s)
      Ohta, S., Tatsumi, Y., Fu j ita, M., Tsurimoto, T., Obuse, C.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 41535-41540

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clamp and clamp loader structures of human checkpoint protein complexes, Rad9-1-1 and Rad17-RFC.2002

    • Author(s)
      Y.Shiomi
    • Journal Title

      Genes Cells 7

      Pages: 861-868

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A proteomics approach to identify PCNA binding proteins in human cell lysates : identification of the human CHL12/RFCs2-5 complex as a novel PCNA binding protein.2002

    • Author(s)
      S.Ohta
    • Journal Title

      J.Biol.Chem. 277

      Pages: 40362-40367

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimetylated DNA.2002

    • Author(s)
      T.Iida
    • Journal Title

      Genes Cells 7

      Pages: 997-1007

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Scheduled Conversion of Replication Complex Architecture at Replication Origins of S.cerevisiae during the cell cycle.2002

    • Author(s)
      R.Tadokoro
    • Journal Title

      J.Biol.Chem. 277

      Pages: 15881-15889

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A proteomics approach to identify PCNA binding proteins in human cell lysates : identification of the human CHL12/RFCs2-5 complex as a novel PCNA binding protein.2002

    • Author(s)
      Ohta, S., Shiomi, Y., Sugimoto, K., Obuse, C., Tsurimoto, T.
    • Journal Title

      J.Biol.Chem. 277

      Pages: 40362-40367

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] T.PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimetylated DNA.2002

    • Author(s)
      I ida, T., Suetake, I., Tajima, S., Morioka, H., Ohta, S., Obuse, C., Tsurimoto
    • Journal Title

      Genes Cells 7

      Pages: 997-1007

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clamp and clamp loader structures of human checkpoint protein complexes, Rad9-1-1 and Rad17-RFC.2002

    • Author(s)
      Shiomi, Y., Shinozaki, A.Nakada, D.Sugimoto, K., Usukura, J., Obuse C.Tsurimoto, T.
    • Journal Title

      Genes Cells 7

      Pages: 861-868

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Scheduled Conversion of Replication Complex Architecture at Replication Origins of S. cerevisiae during the cell cycle.2002

    • Author(s)
      Tadokoro, R., Fujita, M., Miura, H., Shirahige, K., Yoshikawa, H., Tsurimoto, T., Obuse, C.
    • Journal Title

      J.Biol.Chem. 277

      Pages: 15881-15889

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 複製フォーク複合体(細胞周期イラストマップ(中山敬一編))2005

    • Author(s)
      釣本 敏樹
    • Total Pages
      7
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 複製フォーク複合体(細胞周期イラストマップ、中山敬一編)2005

    • Author(s)
      釣本 敏樹
    • Total Pages
      7
    • Publisher
      羊土社
    • Related Report
      2004 Annual Research Report
  • [Book] ゲノム複製メカニズムの理解を目指して(化学フロンティア:ポストゲノムの分子生物学(村上康文編))2003

    • Author(s)
      釣本 敏樹
    • Total Pages
      12
    • Publisher
      化学同人
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] クランプとクランプローダー(ゲノムの複製とその制御(松影昭夫、正井久雄編))2002

    • Author(s)
      釣本 敏樹
    • Total Pages
      10
    • Publisher
      シュプリンガー・フェアーラーク東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] DNA複製伸長過程とその制御(ゲノムの複製とその制御(松影昭夫・正井久雄編))2002

    • Author(s)
      釣本 敏樹
    • Total Pages
      11
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] DNAポリメラーゼδ(生化学誌特集「真核生物のDNAポリメラーゼ・スーパーファミリー」(吉田松年編))2002

    • Author(s)
      釣本 敏樹
    • Total Pages
      5
    • Publisher
      生化学
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Tatsumi, Y.et al.: "The ORC1 cycle in human cells : I. Cell cycle-regulated oscillation of human ORC1"J.Biol.Chem.. 278. 41528-41534 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohta, S.et al.: "The ORC1 cycle in human cells : II. Dynamic changes in the human ORC complex during the cell cycle"J.Biol.Chem.. 278. 41535-41540 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shiomi, Y.et al.: "The reconstituted human Chl12-RFC complex functions as a second PCNA loader"Genes Cells. 9(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 釣本 敏樹: "化学フロンティア:ポストゲノムの分子生物学 ゲノム複製メカニズムの理解を目指して (村上康文編)"化学同人. 12 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Ohta: "A proteomics approach to identify PCNA binding proteins in human cell lysates : identification of the human CHL12/RFCs2-5 complex as a novel PCNA binding protein"J. Biol. Chem.. 277. 40362-40367 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Iida: "PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimetylated DNA"Genes Cells. 7. 997-1007 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Shiomi: "Clamp and clamp loader structures of human checkpoint protein complexes, Rad9-1-1 and Rad17-RFC"Genes Cells. 7. 861-868 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] R.Tadokoro: "Scheduled Conversion of Replication Complex Architecture at Replication Origins of S.cerevisiae during the cell cycle."J. Biol. Chem.. 277. 15881-15889 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 釣本敏樹: "松影昭夫・正井久雄編、「ゲノムの複製とその制御」シュプリンガー・フェラーク東京"クランプとクランプローダー. 10 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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