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Molecular Mechanism on the Regulation of Telomere Structure by Checkpoint Factors

Research Project

Project/Area Number 16570007
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Genetics/Genome dynamics
Research InstitutionNational Institute for Longevity Sciences, National Center for Geriatrics and Gerontology

Principal Investigator

MATSUURA Akira  National Institute for Longevity Sciences, Department of Geriatric Medicine, Section Chief, (研究所)・老年病研究部, 室長 (10272692)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordstelomere / checkpoint / ATM-related proteins / cell cycle / telomerase / DNA double-strand repair / クロマチン免疫沈降法 / DNA末端修復 / MRX複合体 / クロマチン免疫沈隆法
Research Abstract

The telomere is an essential nucleoprotein structure that protects the ends of eukaryotic linear chromosomes. The telomere DNA consists of a unique repeat that is synthesized by telomerase, which is a specialized reverse transcriptase. Due to problems with end-replication, cells that lack telomerase activity are unable to maintain the original telomere length after replication. Therefore, successive rounds of replication in telomerase-deficient cells generate unstable telomere-less chromosomes, which subsequently cause impairment of cell proliferation.
The maintenance of telomeric DNA requires additional factors, at least in yeasts, including a wide range of proteins that are involved in DNA metabolism. Using the chromain immunoprecipitation assay, we showed that Tel1p and Mec1p, PIKK family proteins in Saccharomyces cerevisiae, were recruited to the telomeres at specific times in the cell cycle, in a mutually exclusive manner. Mec1p interacted with the telomeres during late S phase, and this interaction required its own kinase activity, which peaked during the S phase. Moreover, we showed that the MRX (Mre11-Rad50-Xrs2) complex, which functions in DNA double-strand break repair, was recruited to the telomeres in the late S phase, and that its loading was related to the extension of single-stranded telomere tails during this period. MRX was required for the late S phase-specific recruitment of Mec1 (ATR) to the telomeres. Mec1, in turn, contributed to the assembly of the telomerase regulators Cdc13 and Est1 at the telomere ends. Based on these results, we proposed a model for the hierarchical assembly of telomere replication proteins in the late S phase, which involves triggering by the loading of MRX onto the chromosome termini. The recruitment of DNA repair-related proteins to the telomeres at particular times in the cell cycle suggests that the normal terminus of a chromosome is recognized as a DNA double-strand break once per cell cycle.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (20 results)

All 2006 2005 2004

All Journal Article (20 results)

  • [Journal Article] テロメア複製の分子機構:DNA損傷修復過程との類 似性とその意味2006

    • Author(s)
      松浦 彰
    • Journal Title

      蛋白質核酸酵素 51

      Pages: 162-168

    • NAID

      40007110918

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] テロメア複製の分子機構:DNA損傷修復過程との類似性とその意味2006

    • Author(s)
      松浦 彰
    • Journal Title

      蛋白質核酸酵素 51

      Pages: 162-168

    • NAID

      40007110918

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Late S phase-specific recruitment of Mrell complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae.2005

    • Author(s)
      Takaha H, et al.
    • Journal Title

      Mol. Cell 17

      Pages: 573-583

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dimerization of the ATRIP protein through the coiled-coil motif and its implication to the maintenance of stalled replication forks.2005

    • Author(s)
      Itakura E, et al.
    • Journal Title

      Mol. Biol. Cell 16

      Pages: 5551-5562

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] デロメアクロマチンの動的制御とATMファミリー2005

    • Author(s)
      松浦彰
    • Journal Title

      生化学 77

      Pages: 233-240

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Late S phase-specific recruitment of Mrel1 complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae.2005

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

      Mol.Cell 17

      Pages: 573-583

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dimerization of the ATRIP protein through the coiled-coil motif and its implication to the maintenance of stalled replication forks.2005

    • Author(s)
      Itakura E. et al.
    • Journal Title

      Mol.Biol.Cell 16

      Pages: 5551-5562

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] テロメアクロマチンの動的制御とATMファミリー2005

    • Author(s)
      松浦 彰
    • Journal Title

      生化学 77

      Pages: 233-240

    • NAID

      10015548107

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Reciprocal association of the budding yeast ATM-related proteins Tell and Mec1 with telomeres in vivo.2005

    • Author(s)
      Takata H, et al.
    • Journal Title

      Mol.Cell 14

      Pages: 515-522

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Dimerization of the ATRIP protein through the coiled-coil motif and its implication to the maintenance of stalled replication forks.2005

    • Author(s)
      Itakura E, et al.
    • Journal Title

      Mol.Biol.Cell 16

      Pages: 5551-5562

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Late S phase-specific recruitment of Mre11 complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae.2005

    • Author(s)
      Takata H, et al.
    • Journal Title

      Mel.Cell 17

      Pages: 573-583

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reciprocal association of the budding yeast ATM-related proteins Tell and Mecl with telomeres in vivo2004

    • Author(s)
      Takaha H, et al.
    • Journal Title

      Mol. Cell 14

      Pages: 515-522

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ATR-dependent phosphorylation of ATRIP in response to genotoxic stress.2004

    • Author(s)
      Itakura E, et al.
    • Journal Title

      Biochem. Biophys.Res. Commun 323

      Pages: 1197-1202

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amino-terminal domain of ATRIP contributes to intranuclear relocation of the ATR-ATRIP complex following DNA damage.2004

    • Author(s)
      Itakura E, et al.
    • Journal Title

      FEBS Leters 577

      Pages: 289-293

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reciprocal association of the budding yeast ATM-related proteins Tel1 and Mec1 with telomeres in vivo.2004

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

      Mol.Cell 14

      Pages: 515-522

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ATR-dependent phosphorylation of ATRIP in response to genotoxic stress.2004

    • Author(s)
      Itakura E. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 323

      Pages: 1197-1202

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amino-terminal domain of ATRIP contributes to intranuclearrelocation of the ATR-ATRIP complex following DNA damage.2004

    • Author(s)
      Itakura E. et al.
    • Journal Title

      FEBS Lett. 577

      Pages: 289-293

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reciprocal association of the budding yeast ATM-related proteins Tell and Med with telomeres in vivo.2004

    • Author(s)
      Takata H, et al.
    • Journal Title

      Mol.Cell 14

      Pages: 515-522

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ATR-dependent phosphorylation of ATRIP in response to genotoxic stress.2004

    • Author(s)
      Itakura E, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 323

      Pages: 1197-1202

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Amino-terminal domain of ATRIP contributes to intranuclear relocation of the ATR-ATRIP complex following DNA damage.2004

    • Author(s)
      Itakura E, et al.
    • Journal Title

      FEBS Letters 577

      Pages: 289-293

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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