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Genome-wide identification of DNA replication origin sequences in human cells

Research Project

Project/Area Number 16K12595
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Risk sciences of radiation and chemicals
Research InstitutionKyoto University

Principal Investigator

Takeda Shunichi  京都大学, 医学研究科, 教授 (60188191)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsDNA複製 / 複製ポリメラーゼδ / 複製ポリメラーゼε / 複製起点 / シタラビン(Cytarabine) / 変異 / ヒト細胞
Outline of Final Research Achievements

DNA replication is initiated from replication origin sequences in the genome. Although the locations of all origins have been identified in yeast species, the replication origins have not yet been mapped in the human genome. The aim of this research is to map all origin sequences in human cells, TK6 B cell line. DNA polymerases δ and ε (Polδ and Polε) play roles in lagging-strand and leading-strand replication, respectively. Prof. Tony Carr (Sussex, UK) mapped all replication origins in the yeast genome by determining the exact locations of polymerase switching during lagging and leading strand replication. We had followed this method, which used the Polδ and Polε mutants that frequently mis-incorporates ribonucleotides. We then learned that such mutant polymerases are highly cytotoxic to human cells. We have established another method, and already sent mutant cells to a collaborator, Prof. Carr in Sussex, UK. They will map all replication origin sequences in the near future.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2017 2016 Other

All Int'l Joint Research (4 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 3 results)

  • [Int'l Joint Research] Sussex University/MRC, Laboratory of Molecular Biology(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] NIH/National Cancer Institute(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Naional Institutes of Health(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] MRC分子生物学研究所(英国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] The dominant role of proofreading exonuclease activity of replicative polymerase ε in cellular tolerance to cytarabine (Ara-C).2017

    • Author(s)
      Tsuda M, Terada K, Ooka M, Kobayashi K, Sasanuma H, Fujisawa R, Tsurimoto T, Yamamoto J, Iwai S, Kadoda K, Akagawa R, Huang SN, Pommier Y, Sale JE, Takeda S, Hirota K.
    • Journal Title

      Oncotarget

      Volume: in press Issue: 20 Pages: 33457-33474

    • DOI

      10.18632/oncotarget.16508

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] In vivo evidence for translesion synthesis by the replicative DNA polymeraseδ2016

    • Author(s)
      Hirota K, Tsuda M, Sale J, Takeda S
    • Organizer
      The 10th 3R Symposium
    • Place of Presentation
      島根県松江市
    • Year and Date
      2016-11-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] In vivo evidence for translation synthesis by the replicative DNA polymerase delta2016

    • Author(s)
      Hirota K, Tsuda M, Sale J, Takeda S
    • Organizer
      DNA Polymerases Meeting
    • Place of Presentation
      Biarritz, France
    • Year and Date
      2016-10-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] SUMO E3 ligases PIAS1 and PIAS4 facilitate template switching by enhancing SUMOylation of PCNA2016

    • Author(s)
      Mohiuddin, Evans TJ, Takeda S
    • Organizer
      Abcam Mechanisms of Recombination 2016
    • Place of Presentation
      Alicante, Spain
    • Year and Date
      2016-05-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2022-06-16  

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