• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Defective homologous recombination repair and carcinogenesis

Research Project

Project/Area Number 12213088
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

MIYAGAWA Kiyoshi  Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (40200133)

Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥50,700,000 (Direct Cost: ¥50,700,000)
Fiscal Year 2004: ¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2003: ¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2002: ¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2001: ¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2000: ¥9,000,000 (Direct Cost: ¥9,000,000)
Keywordshomologous recombination / genome instability / DNA repair / breast cancer / chromosomal aberration
Research Abstract

A defect in homologous recombination repair has been implicated in carcinogenesis because hereditary breast cancer genes BRCA were shown to play an important role in homologous recombination repair. We have investigated a molecular mechanism of homologous recombination repair in human cells. Rad54B, a gene identified as a novel recombination repair gene, exhibits the double-strand DNA-dependent ATPase activity and is required for gene targeting in human cells. XRCC3, a member of Rad51 paralog, is required for homologous recombination via sister chromatids. Additionally, XRCC3 prevents DNA rereplication and endoreduplication, thereby ensuring chromosome integrity. The T241M variant, a genetic polymorphism implicated in cancer risk, exhibits intact recombination repair, but fails to prevent endoreduplication, suggesting that an increase in endoreduplication is associated with cancer risk. A similar phenotype is observed in a resolvase gene Mus81-deficient cells. This aberration is caused by Cyclin B/Cdc2 inhibition by Chk2 activation in response to DNA damage. Thus, the recombination machinery is tightly associated with DNA replication and cell-cycle regulation. This finding suggests that a defect in the DNA metabolic network induces chromosome instability.

Report

(6 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (34 results)

All 2005 2004 2003 2002 2001 2000 Other

All Journal Article (18 results) Publications (16 results)

  • [Journal Article] Gene trap mutagenesis-based forward genetic approach reveals that the tumor suppressor OVCA1 is a component of the biosynthetic pathway of diphtamide on elongation factor-22005

    • Author(s)
      Nobukuni, Y.
    • Journal Title

      J.Biol.Chem. (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene trap mutagenesis-based forward genetic approach reveals that the tumor suppressor OVCA1 is a component of the biosynthetic pathway of diphtamide on elongation factor-2.2005

    • Author(s)
      Nobukuni, Y.
    • Journal Title

      J.Biol.Chem. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene trap mutagenesis-based forward genetic approach reveals that the tumor suppressor OVCA1 is a component of the biosynthetic pathway of diphtamide on elongation factor-22005

    • Author(s)
      Nobukuni, Y.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 10572-10577

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Structural basis for octameric ring formation and DNA interaction of the human homologous-pairing protein Dmcl2004

    • Author(s)
      Kinebuchi, T.
    • Journal Title

      Mol.Cell 14

      Pages: 363-374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] XRCC3 deficiency results in a defect in recombination and increased endoreduplication in human cells2004

    • Author(s)
      Yoshihara, T.
    • Journal Title

      EMBO J. 23

      Pages: 670-680

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Structural basis for octameric ring formation and DNA interaction of the human homologous-pairing protein Dmc1.2004

    • Author(s)
      Kinebuchi, T.
    • Journal Title

      Mol.Cell 14

      Pages: 363-374

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] XRCC3 deficiency results in a defect in recombination and increased endoreduplication in human cells.2004

    • Author(s)
      Yoshihara, T.
    • Journal Title

      EMBO J. 23

      Pages: 670-680

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Structural basis for octameric ring formation and DNA interaction of the human homologous-pairing protein Dmc12004

    • Author(s)
      Kinebuchi, T.
    • Journal Title

      Mol.Cell 14

      Pages: 363-374

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A new system for laser-UVA-microirradiation of living cells.2003

    • Author(s)
      Walter, J.
    • Journal Title

      J.Microscopy 209

      Pages: 71-75

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human Rad54B is a double-stranded DNA-dependent ATPase and has biochemical properties different from its structural homolog in yeast, Tid1/Rdh542002

    • Author(s)
      Tanaka, K.
    • Journal Title

      Nucleic Acids Res. 30

      Pages: 1346-1353

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A role for RAD54B in homologous recombination in human cells2002

    • Author(s)
      Miyagawa, K.
    • Journal Title

      EMBO J. 21

      Pages: 175-180

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human Rad54B is a double-stranded DNA-dependent ATPase and has biochemical properties different from its structural homolog in yeast, Tid1/Rdh54.2002

    • Author(s)
      Tanaka, K.
    • Journal Title

      Nucleic Acids Res. 30

      Pages: 1346-1353

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A role for RAD54B in homologous recombination in human cells.2002

    • Author(s)
      Miyagawa, K.
    • Journal Title

      EMBO J. 21

      Pages: 175-180

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Alterations of the double-strand break repair gene MRE11 in cancer2001

    • Author(s)
      Fukuda, T.
    • Journal Title

      Cancer Res. 61

      Pages: 23-26

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Alterations of the double-strand break repair gene MRE11 in cancer.2001

    • Author(s)
      Fukuda, T.
    • Journal Title

      Cancer Res. 61

      Pages: 23-26

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Deoxycytidyl transferase activity of the human REV1 protein is closely associated with the conserved polymerase domain.2001

    • Author(s)
      Masuda, Y.
    • Journal Title

      J.Biol.Chem. 276

      Pages: 15051-15058

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Evidence for RAD51L1/HMGIC fusion in the pathogenesis of uterine leiomyoma.2001

    • Author(s)
      Takahashi, T.
    • Journal Title

      Genes Chromosomes Cancer 30

      Pages: 196-201

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel human Rad54 homologue, Rad54B, associates with Rad51.2000

    • Author(s)
      Tanaka, K.
    • Journal Title

      J.Biol.Chem. 275

      Pages: 26316-26321

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yoshihara, T.: "XRCC3 deficiency results in a defect in recombination and increased endoreduplication in human cells"The EMBO journal. 23(3). 670-680 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishida, M.: "Mnk1 is required for angiotensin II-induced protein systhesis in vascular smooth muscle cells"Circulation Research. 93(12). 1218-1224 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Walter, J.: "A new system for laser-UVA-microirradiation of living cells"J. Microscopy. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka, K.: "Human Rad54B is a doluble-stranded DNA-dependent ATPase and has biocbemical properties different from its structural homolog in yeast, Tid1/Rdb54"Nucleic. Acids Res.. 30(6). 1346-1353 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyagawa, K.: "A role for RAD54B in homologous recombination in human cells"EMBO J.. 21(1&2). 175-180 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsurnga, T.: "Ocular development-associated gene (ODAG), a novel gene highly expressed in ocular development"Gene. 290(1・2). 125-130 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyagawa, K.: "A role for RAD54B in homologous recombination in human cells"The EMBO Journal. 21(1-2). 175-180 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazo, T.: "Human RAD54B is a double-stranded DNA-dependent ATPase and has biochemical properties different from its structual homologue in yeast, Tidl/Rdh54"Nucleic Acids Research. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masuda, Y.: "Deoxycytidyl transferase activity of the human REV1 protein is closely associated with the conserved polymerase domain"The Journal of Biological Chemistry. 276(18). 15051-15058 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukuda, T.: "Alterations of the double-strand break repair gene MRE11 in cancer"Cancer Reseach. 61(1). 23-26 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi, T.: "Evident for RAD51L1/HMGIC fusion in the pathogenesis of uterine leiomyoma"Genes Chromosomes Cancer. 30(2). 196-201 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masuda,Y.: "Deoxycytidyl transferase activity of the human Rev1 protein is closely associated with the conserved polymerase domain"J.Biol.Chem.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukuda,T.: "Alterations of the double-strand break repair gene MRE11 in cancer"Cancer Res.. 61(1). 23-26 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi,T.: "Evidence for RAD51L1/HMGIC fusion in the pathogenesis of uterine leiomyoma"Genes Chromosomes Cancer. 30(2). 196-201 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka,K.: "A novel human Rad54 homologue, Rad54B, associates with Rad51"J.Biol.Chem.. 275(34). 26316-26321 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi,T.: "Mutation analysis of the WT1 gene in secondary leukemia"Leukemia. 14(7). 1316-1317 (2000)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi