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Chromosome instability and homologous recombination

Research Project

Project/Area Number 13141204
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNara Institute of Science and Technology

Principal Investigator

UMEZU Keiko  Nara Institute of Science and Technology, Graduate School of Biological Sciences, Assistant Professor, バイオサイエンス研究科, 助手 (20223612)

Co-Investigator(Kenkyū-buntansha) MORITA Takashi  Osaka City University, Medical School, Professor, 大学院医学研究科, 教授 (70150349)
Project Period (FY) 2001 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥41,700,000 (Direct Cost: ¥41,700,000)
Fiscal Year 2005: ¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2004: ¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 2003: ¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 2002: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2001: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordschromosome aberration / genome rearrangement / genetic recombination / DNA damage / DNA repair
Research Abstract

Our goal is to understand the molecular mechanisms of cellular processes that protect genome integrity against assaults arising endogenously. [Umezu] To understand the cellular processes involved in genome maintenance, we have developed an assay that analyzes the genetic events responsible for loss of a heterozygous marker (LOH) in yeast diploid cells. This assay allows the quantitative identification of various genetic alterations including chromosome loss, different types of chromosome rearrangements, and point mutations. By exploiting the molecular genetic systems to determine factors involved in genome maintenance, we showed that homologous recombination plays both positive and negative roles in the maintenance of genome stability. In other words, spontaneous DNA lesions capable of triggering homologous recombination occur at a strikingly high frequency throughout the genome during normal cell growth; the majority of lesions are processed precisely through sister chromatid recombination, and a part of the process leads to genetic alterations. We also found that homologous recombination is regulated at multiple steps in such a way as to suppress genome instability, presumably to control its dual roles. The focus of our current studies is on understanding how homologous recombination is regulated in a way to suppress genome instability and we are examining the effects of a defect in SGSJ, SRS2 or RDH54 on genome maintenance. The mutants have broader effects than expected from the previous studies, suggesting new roles of these genes in chromosome maintenance, which we are now investigating. [Morita] We have studied on mouse FDH1 gene, and showed that the gene product is expressed in testis germ cells, especially the cells in the pachytene stage where meiotic homologous recombination takes place. Now, we are investigating the effect of FDHp on the stability of various recombination proteins by RNAi method. We also under construction of FDH1 KO mouse.

Report

(6 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (39 results)

All 2005 2004 2003 2002 Other

All Journal Article (22 results) Patent(Industrial Property Rights) (5 results) Publications (12 results)

  • [Journal Article] RNA interference in spermatogenesis in mice.2005

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

      Dev. Biol. 15・282

      Pages: 524-534

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] RNA interference in spermatogenesis in vivo.2005

    • Author(s)
      Shoji, M., et al.
    • Journal Title

      Dev. Biol. 15

      Pages: 524-534

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] RNA interference in spermatogenesis in mice.2005

    • Author(s)
      M.Shoji
    • Journal Title

      Dev. Biol. 15・282

      Pages: 524-534

    • Related Report
      2005 Annual Research Report
  • [Journal Article] RNA interference in spermatogenesis in vivo2005

    • Author(s)
      M.Shoji
    • Journal Title

      Dev.Biol. (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Control of radiosensitivity of F9 mouse teratocarcinoma cells by regulation of histone H2AX gene expression using a tetracycline turn-off system.2004

    • Author(s)
      Yoshida, K. et al.
    • Journal Title

      Can. Res. 64

      Pages: 4131-4136

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] p53 protein interacts specifically with the meiosis-specific mammalian RecA-like protein DMC1 in meiosis.2004

    • Author(s)
      Habu, T. et al.
    • Journal Title

      Carcinogenesis 25

      Pages: 889-893

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Control of Radiosensitivity of F9 Mouse Teratocarcinoma Cells Regulation of Histone H2AX Gene Expression using a Tetracycline Turn-Off System.2004

    • Author(s)
      Yoshida, K. et al.
    • Journal Title

      Cancer Res. 64

      Pages: 4131-4136

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] p53 protein interacts specifically with the meiosis-specific mammalian RecA-like protein DMC1 in meiosis.2004

    • Author(s)
      Habu, T., et al.
    • Journal Title

      Carcinogenesis 25

      Pages: 889-893

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Control of radiosensitivity of F9 mouse teratocarcinoma cells by regulation of histone H2AX gene expression using a tetracycline turn-off system2004

    • Author(s)
      K.Yoshida
    • Journal Title

      Cancer Res. 64

      Pages: 4131-4236

    • Related Report
      2004 Annual Research Report
  • [Journal Article] p53 protein interacts specifically with the meiosis-specific mammalian RecA-like protein DNC1 in meiosis2004

    • Author(s)
      T.Habu
    • Journal Title

      Carcinogenesis 25

      Pages: 889-893

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Positive and negative roles of homologous recombination in the maintenance of genome stability in Saccharomyces cerevisiae.2003

    • Author(s)
      Yoshida, J. et al.
    • Journal Title

      Genetics 164

      Pages: 31-46

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression and Radiation-induced Phosphorylation of Histone H2AX in Mammalian Cells.2003

    • Author(s)
      Yoshida, K. et al.
    • Journal Title

      J. Rad. Res. 44

      Pages: 47-51

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Positive and negative roles of homologous recombination in the maintenance of genome stability in Saccharomyces cerevisiae.2003

    • Author(s)
      Yoshida J., et al.
    • Journal Title

      Genetics 164

      Pages: 31-46

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression and Radiation-induced Phosphorylation of Histone H2AX in Mammalian Cells.2003

    • Author(s)
      Yoshida, K., et al.
    • Journal Title

      J. Rad. Res. 44

      Pages: 47-51

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structural analysis of aberrant chromosomes that occur spontaneously in diploid Saccharomyces cerevisiae. Retrotransposon Ty1 plays a crucial role in chromosomal rearrangements.2002

    • Author(s)
      Umezu, K. et al.
    • Journal Title

      Genetics 307

      Pages: 97-110

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Induction of instability of p34(cdc2) expression by treatment with cisplatin (CDDP) in mouse teratocarcinoma F9 cells.2002

    • Author(s)
      Doi, T.et al.
    • Journal Title

      Cancer Lett. 176

      Pages: 75-80

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of RAD9-dependent damage checkpoint control in arrest of cell cycle, induction of cell death, and chromosome instability caused by defects in origin recognition complex in Saccharomyces cerevisiae.2002

    • Author(s)
      Watanabe, K. et al.
    • Journal Title

      Eukaryotic Cell 1

      Pages: 200-212

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Elevated incidence of loss of heterozygosity(LOH) in an sgs1 mutant of Saccharomyces cerevisiae.2002

    • Author(s)
      Ajima, J. et al.
    • Journal Title

      Mutation Research 504

      Pages: 157-172

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structural analysis of aberrant chromosomes that occur spontaneously in diploid Saccharomyces cerevisiae : Retrotransposon Tyl plays a crucial role in chromosomal rearrangements.2002

    • Author(s)
      Umezu K., et al.
    • Journal Title

      Genetics 160

      Pages: 97-110

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Induction of instability of p34(cdc2) expression by treatment with cisplatin (CDDP) in mouse teratocarcinoma F9 cells.2002

    • Author(s)
      Doi T, et al.
    • Journal Title

      Cancer Lett. 176

      Pages: 75-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of RAD9-dependent damage checkpoint control in arrest of cell cycle, induction of cell death, and chromosome instability caused by defects in origin recognition complex in Saccharomyces cerevisiae.2002

    • Author(s)
      Watanabe K., et al.
    • Journal Title

      Eukaryotic Cell 1

      Pages: 200-212

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Elevated incidence of loss of heterozygosity (LOH) in an sgsl mutant of Saccharomyces cerevisiae : Roles of yeast RecQ helicase in suppression of aneuploidinterchromosomal rearrangement, and the simultaneous incidence of both events during mitotic growth.2002

    • Author(s)
      Ajima J., et al.
    • Journal Title

      Mutation Research 504

      Pages: 157-172

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 相同組換反応に関与するマウス遺伝子2004

    • Inventor(s)
      森田隆
    • Industrial Property Rights Holder
      森田隆
    • Filing Date
      2004
    • Acquisition Date
      2004
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 相同組換反応に関与するマウス遺伝子2004

    • Inventor(s)
      森田 隆
    • Industrial Property Rights Holder
      森田 隆
    • Filing Date
      2004
    • Acquisition Date
      2004
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] RNAiによる新規治療法および治療剤2002

    • Inventor(s)
      森田隆
    • Industrial Property Rights Holder
      森田隆
    • Industrial Property Number
      2002-340183
    • Filing Date
      2002
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] RNAiによる新規治療法および治療薬2002

    • Inventor(s)
      森田 隆
    • Industrial Property Rights Holder
      森田 隆
    • Industrial Property Number
      2002-340183
    • Filing Date
      2002
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] RNAiによる新規治療法および治療剤2002

    • Inventor(s)
      森田 隆
    • Industrial Property Rights Holder
      森田 隆
    • Industrial Property Number
      2002-340183
    • Filing Date
      2002
    • Related Report
      2004 Annual Research Report
  • [Publications] Yoshida, J. et al.: "Positive and negative roles of homologous recombination in the maintenance of genome stability in Saccharomyces cerevisiae."Genetics. 164. 31-46 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshida, J. et al.: "Expression and Radiation-induced Phosphorylation of Histone H2AX in Mammalian Cells."J.Rad.Res.. 44. 47-51 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Habu, T. et al.: "p53 protein interacts specifically with the meiosis-specific mammalian RecA-like protein DMC1 in meiosis."Carcinogenesis. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe, K. et al.: "Involvement of RAD9-dependent damage checkpoint control in arrest of cell cycle, induction of cell death, and chromosome instability caused by defects in origin recognition complex in Saccharomyces cerevisiae"Eukaryotic Cell. 1. 200-212 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ajima, J. et al.: "Eleveted incidence of loss of heterozygosity (LOH) in an sgs1 mutant of Saccharomyces cerevisiae"Mutation Research. 504. 157-172 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida, J. et al.: "Positive and negative roles of homologous recombiation in the maintenance of genome stability in Saccharomyces cerevisiae"Genetics. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Doi, T.et al.: "Induction of instability of p34(cdc2) expression by treatment with cisplatin (CDDP) in mouse teratocarcinoma F9 cells"Cancer Lett.. 176. 75-80 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida, K. et al.: "Expression and Radiation-induced Phosphorylation of Histone H2AX in Mammalian Cells"J. Rad. Res.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Umezu, K. et al.: "Structural analysis of aberrant chromosomes that occur spontaneously in diploid Saccharomyces cerevisiae : Retrotransposon Ty1 plays a crucial role in chromosomal rearrangements"Genetics. 307. 97-110 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watanabe, K. et al.: "Involvement of RAD9-dependent damage checkpoint control in arrest of cell cycle, induction of cell death, and chromosome instability caused by defects in origin recognition complex in Saccharomyces cerevisiae"Eukaryotic Cell. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ajima, J. et al.: "Eleveted incidence of loss of heterozygosity(LOH) in an sgs1 mutant of Saccharomyces cerevisiae"Mutation Research. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Doi, T.et al.: "Induction of instability of p34(cdc2) expression by treatment with cisplatin (CDDP) in mouse teratocarcinoma F9 cells"Cancer Lett.. 176. 75-80 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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