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Mechanism that govern the intracellular dynamics and elimination of extrachromosomal genetic element

Research Project

Project/Area Number 14340238
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 遺伝
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

SHIMIZU noriaki  Hiroshima University, Faculty of Integrated Arts and Sciences, Associate Professor, 総合科学部, 助教授 (10216096)

Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥3,700,000 (Direct Cost: ¥3,700,000)
KeywordsGene Amplification / Extrachromosomal Element / Replication Initiation Region / Matrix Attachment Region / Micronuclei / DMs / HSR / 生細胞可視化技術 / 2本鎖切断 / DNA修復 / 細胞周期チェックポイント / 細胞内動態 / BFB cycle / anaphase bridge / 複製 / 哺乳動物複製起点 / ポリ(A)付加配列 / 複製フォーク阻害配列
Research Abstract

Gene amplification plays a pivotal role in malignant transformation of human cells. The amplified genes localize either at extrachromsomal DMsorchromosomal HSR. DMs are autonomously replicating acentric extrachromosomal chromatin. We previously found that the plasmid having a mammalian replication initiation region and a matrix attachment region efficiently generated DMs and/or HSR, de novo. We also found that the human cancer cells lose tumor phenotype and normalized, if the DMs were eliminated. The elimination was mediated by the specific incorporation of DMs into the cytoplasmic micronuclei. The inclusion into the micronuclei depended on a novel intracellular behavior of DMs during the cell cycle progression. The behavior and the elimination of DMs is common among abroad spectrum of autonomously replicating extrachromosomal genetic element. In this study, we advanced our understanding upon the molecular mechanism that govern the behavior and the elimination of extrachromosomal element. Furthermore, we applied the understanding to the basic biological study on the nucleus, as well as to the technology to produce recombinant protein. Specifically, we did the following studies, and obtained many achievements from each of these. 1) Study on the molecular mechanism underlying the intracellular behavior of DMs that led to the inclusion into the micronuclei. 2) Study on the behavior and the elimination of DNA molecule placed at the nucleus or the cytoplasm by microinjection. 3) Study on the mechanism of gene amplification mediated by the autonomously replicating extrachromosomal molecule. 4) Study on the gene expression from the amplified genetic region. 5) Study on the application of our efficient gene amplification system to the technology on recombinant protein production. 6) Study on the functional structure of the interphase cell nucleus by using a novel feature of HSR that was generated by our plasmid-based amplification system.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (13 results)

All 2005 2004 2003 Other

All Journal Article (10 results) Patent(Industrial Property Rights) (2 results) Publications (1 results)

  • [Journal Article] When, where and how the bridge brgaks : Anaphase bridge breakage plays a crucial role in gene amplification and HSR-generation.2005

    • Author(s)
      N.Shimizu et al.
    • Journal Title

      Experimental Cell Research 302 ・ 2

      Pages: 233-243

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tracking of microinjected DNA in live cells reveals the intracellular behavior and elimination of extrachromosomal genetic materia1.2005

    • Author(s)
      N.Shimizu et al.
    • Journal Title

      Nucleic Acids Research 33 ・ 19

      Pages: 6269-6307

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] When, where and how the bridge breaks : Anaphase bridge breakage plays a crucial role in gene amplification and HSR-generation.2005

    • Author(s)
      Noriaki Shimizu et al.
    • Journal Title

      Experimental Cell Research Vol 302, no. 2

      Pages: 233-243

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tracking of microinjected DNA in live cells reveals the intracellular behavior and elimination of extrachromosomal genetic material.2005

    • Author(s)
      Noriaki Shimizu et al.
    • Journal Title

      Nucleic Acids Research vol.33, no.19

      Pages: 6296-6307

    • NAID

      120000882175

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] When, where and how the bridge breaks : Anaphase bridge breakage plays a crucial role in gene amplification and HSR-generation.2005

    • Author(s)
      N.Shimizu et al.
    • Journal Title

      Experimental Cell Research 302・2

      Pages: 233-243

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Macroscopic folding and replication of the homogeneously staining region in late S phase leads to the appearance of replication bands in mitotic chromosomes.2004

    • Author(s)
      N.Shimizu et al.
    • Journal Title

      Journal of Cell Science 117 ・ 22

      Pages: 5303-5312

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Macroscopic folding and replication of the homogeneously staining region in late S phase leads to the appearance of replication bands in mitotic chromosomes.2004

    • Author(s)
      Noriaki Shimizu et al.
    • Journal Title

      Journal of Cell Science Vol. 117, no. 22

      Pages: 5303-5312

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Macroscopic folding and replication of the homogeneously staining region in late S phase leads to the appearance of replication bands in mitotic chromosomes.2004

    • Author(s)
      N.Shimizu, K.Shingaki
    • Journal Title

      Journal of Cell Science 117・22

      Pages: 5303-5312

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Amplification of plasmids containing a mammalian replication initiation region is mediated by controllable conflict between replication and transcription2003

    • Author(s)
      N.Shimizu et al.
    • Journal Title

      Cancer Research 63 ・ 17

      Pages: 5281-5290

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Amplification of plasmids containing a mammalian replication initiation region is mediated by controllable conflict between replication and transcription.2003

    • Author(s)
      Noriaki Shimizu et al.
    • Journal Title

      Cancer Research vol.63, no.17

      Pages: 5281-5291

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 「研究成果報告書概要(和文)」より2005

    • Inventor(s)
      清水典明
    • Industrial Property Rights Holder
      広島大学二
    • Industrial Property Number
      2004-334984
    • Filing Date
      2005-11-15
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 特許2004

    • Inventor(s)
      清水 典明
    • Industrial Property Rights Holder
      広島大学長
    • Industrial Property Number
      2004-334984
    • Filing Date
      2004-11-18
    • Related Report
      2004 Annual Research Report
  • [Publications] N.Shimizus et al.: "Amplification of plasmids containing a mammalian replication initiation region is mediated by controllable conflict between replication and transcription"Cancer Research. 63・17. 5281-5290 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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