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Telomere maintenance by chromosome damage response mechanism

Research Project

Project/Area Number 16570145
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionKyoto University

Principal Investigator

NABETANI Akira  Kyoto University, Graduate School of Biostudies, Instructor, 大学院・生命科学研究科, 助手 (40334495)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA Fuyuki  Kyoto University, Graduate School of Biostudies, Professor, 大学院・生命科学研究科, 教授 (30184493)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsTelomere / Damage checkpoint / Recombination / Chromosome / 損傷チェックポイント機構 / 複製 / ALT / 細胞周期 / 染色体複製
Research Abstract

We analyzed the role of the damage checkpoint mechanism in the telomere maintenance mechanism of the ALT cells, which are independent from telomerase. At first, we found that checkpoint Rad protein group (the Rad9-Hus1-Rad1 clamp complex and the Rad17-RFC loader complex) were colocalized with telomeric DNA to form the ALT-associated PML body (APB) in the cell nucleus. On the other hand, phosphorylated Rad17 and γ-H2AX, markers for DNA damage, were also localized at a part of APB. This result suggests that the damage response of the ALT cell telomere could be divided into two stages : the localization of checkpoint Rad protein and the activation of ATM/ATR kinases. Incorporation of BrdU at a part of APB was observed and this is sensitive to caffeine, an inhibitor to ATM/ATR. This suggests that the activation of the damage response mechanism be indispensable to the telomere reproduction by the ALT cell. We next examined a structural feature of telomere DNA of ALT cells, to clarify why the damage response is activated. From Southern hybridization analyses, we found the single-stranded DNA structure of the telomere DNA specifically in ALT cells. This suggests that the damaged telomeric DNA, such as nick and gap, exists in ALT cell, and this structure could be maintained. We hypothesized that the stall of the replication fork at telomere might induce recombination and this would be the mechanism for the lengthening of telomere in the ALT cells.

Report

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

    (8 results)

All 2006 2005 2004

All Journal Article (8 results)

  • [Journal Article] Cell-cycle-dependent Xenopus TRF1 recruitment to telomere chromatin regulated by Polo-like kinase.2006

    • Author(s)
      Nishiyama A, Muraki K, Saito M, Ohsumi K, Kishimoto T, Ishikawa F.
    • Journal Title

      EMBO J. 25(3)

      Pages: 575-584

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Alterations of DNA and chromatin structures at telomeres and genetic instability in mouse cells defective in DNA polymerase α2005

    • Author(s)
      Nakamura, M., Nabetani, A., Mizuno, T., Hanaoka, F., Ishikawa, F.
    • Journal Title

      Mol. Cell. Biol. 25・24

      Pages: 11073-11088

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Alterations of DNA and chromatin structures at telomeres and genetic instability in mouse cells defective in DNA polymerase α2005

    • Author(s)
      Nakamura, M., Nabetani, A., Mizuno, T., Hanaoka, F., Ishikawa, F.
    • Journal Title

      Mol.Cell.Biol. 25(24)

      Pages: 11073-11088

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Alterations of DNA and chromatin structures at telomeres and genetic instability in mouse cells defective in DNA polymerase α.2005

    • Author(s)
      Nakamura M, Nabetani A, Mizuno T, Hanaoka F, Ishikawa F.
    • Journal Title

      Mol Cell Biol. 25(24)

      Pages: 11073-11088

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells.2005

    • Author(s)
      Okumura-Nakanishi, S., Saito, M., Niwa, H., Ishikawa, F.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 5307-5317

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Localization of hRad9, hHus1, hRad1, and hRad17 and caffeine-sensitive DNA replication at alternative lengthening of telomeres-associated promyelocytic leukemia body2004

    • Author(s)
      Nabetani, A., Yokoyama, O., Ishikawa, F.
    • Journal Title

      J. Biol. Chem. 279・24

      Pages: 25849-25857

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Localization of hRad9, hHus1, hRad1, and hRad17 and caffeine-sensitive DNA replication at alternative lengthening of telomeres-associated promyelocytic leukemia body2004

    • Author(s)
      Nabetani, A., Yokoyama, O., Ishikawa, F
    • Journal Title

      J.Biol.Chem. 279(24)

      Pages: 25849-25857

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Localization of hRad9, hHus1, hRad1, and hRad17 and caffeine-sensitive DNA replication at the alternative lengthening of telomeres-associated promyelocytic leukemia body.2004

    • Author(s)
      Nabetani, A., Yokoyama, O., Ishikawa, F.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 25849-25857

    • Related Report
      2004 Annual Research Report

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

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