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2004 Fiscal Year Final Research Report Summary

Functional analysis of genes involved in maintenance of chromosome stability and homologous recombination

Research Project

Project/Area Number 12213059
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKawasaki Medical School

Principal Investigator

TAKATA Minoru  Kawasaki Medical School, Dept of Immunology and Molecular Genetics, Professor, 医学部, 教授 (30281728)

Co-Investigator(Kenkyū-buntansha) MATSUSHITA Nobuko  Kawasaki Med Sch, Dept of Immunol and Mol Genet, Research Associate, 医学部, 助手 (30333222)
KITAO Hiroyuki  Kawasaki Med Sch, Deptcf Immunol and Mol Genet, Research Associate, 医学部, 助手 (30368617)
HIRANO Seiki  Kawasaki Med Sch, Dept of Immunol and Mol Genet, Research Associate, 医学部, 助手 (20368616)
KIURA Katsuyuki  Okayama University Med Sch, 2nd Dept of Med, Assistant Professor, 大学院医歯薬総合研究科, 講師 (10243502)
Project Period (FY) 2000 – 2004
Keywordshomologous recombination / DNA repair / DT 40 cells / Rad51 paralogs / Fanconi anemia / sister chromatid exchanges / 姉妹染色分体交換
Research Abstract

DNA repair mediated by homologous recombination (HR) is an important mechanism in promoting genome stability and preventing carcinogenesis. In this project, we disrupted putative HR regulators including five Rad51 paralogs and Fanconi anemia genes in chicken cell line DT40.
(1) Cells lacking each of Rad51 paralogs all displayed very similar HR defects such as cisplatin sensitivity, increased chromosomal aberrations, and loss of Rad51 focus formation or gene targeting efficiencies. Since Rad51 paralogs interact with each other, these results suggest that Rad51 paralogs work together as a functional unit in mediating HR reactions through Rad51.
(2) We found that Rad52 (an HR factor) and Xrcc3 (one of Rad51 paralogs) exhibited synthetic lethality in DT40 cells, indicating that there are some overlapping functions between these two molecules.
(3) DT40 mutants lacking FA genes displayed HR defects such as decreased gene targeting efficiencies, a decreased gene conversion frequency at immunoglobulin locus, and impaired HR repair of restriction enzyme-induced chromosonal double strand breaks. These results were the first formal demonstration of the role of FA genes in HR.
(4) We showed epistasis between BLM helicase and the FA pathway in terms of SCE frequency and sensitivities to MMC or cisplatin. BLM helicase seems to be one of the effector molecules of the FA pathway.

  • Research Products

    (14 results)

All 2005 2004 2003 2002 2001

All Journal Article (14 results)

  • [Journal Article] Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM.2005

    • Author(s)
      Hirano S.et al.
    • Journal Title

      EMBO J. 26;24(2)

      Pages: 418-427

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination.2005

    • Author(s)
      Yamamoto K.et al.
    • Journal Title

      Mol Cell Biol 25(1)

      Pages: 34-43

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination.2005

    • Author(s)
      Yamamoto K. et al.
    • Journal Title

      Mol Cell Biol. Jan 25(1)

      Pages: 34-43

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] DNA crosslink repair protein SNM1A interacts with PIAS1 in nuclear focus formation.2004

    • Author(s)
      M Ishiai.et al.
    • Journal Title

      Mol.Cell Biol. 24(24)

      Pages: 5421-5430

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM.2004

    • Author(s)
      Hirano S. et al.
    • Journal Title

      EMBO J. 2005 Jan 26 24(2)

      Pages: 418-27

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] (2004)-DNA crosslink repair protein SNM1A interacts with PIAS1 in nuclear focus formation.2004

    • Author(s)
      M.Ishiai et al.
    • Journal Title

      Mol Cell Biol. 24(24)

      Pages: 10733-41

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells.2003

    • Author(s)
      Yamamoto K.et al.
    • Journal Title

      Mol.Cell Biol. 23

      Pages: 5421-5430

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Fanconi anemia FANCG protein in mitigating radiation-and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells.2003

    • Author(s)
      Yamamoto K. et al.
    • Journal Title

      Mol Cell Biol. 23

      Pages: 5421-5430

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells.2002

    • Author(s)
      Tauchi H. et al.
    • Journal Title

      Nature. 420

      Pages: 93-98

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells.2001

    • Author(s)
      Tauchi H.et al.
    • Journal Title

      Nature 420

      Pages: 93-98

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Conserved domains in the chicken homologue of BRCA2.2001

    • Author(s)
      Takata M. et al.
    • Journal Title

      Mol Cell Bio1. 21

      Pages: 2858-2866

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs.2001

    • Author(s)
      Takata M. et al.
    • Journal Title

      Nature. 412

      Pages: 921-926

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ablation of XRCC2/3 transforms immunoglobulin V gene conversion into somatic hypermutation.2001

    • Author(s)
      Sale JE. et al.
    • Journal Title

      Nature. 412

      Pages: 921-926

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells.2001

    • Author(s)
      A.Fujimori et al.
    • Journal Title

      EMBO J. 20

      Pages: 5513-5520

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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