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Elucidation of novel mechanism to lead DNA over-replication

Research Project

Project/Area Number 16H06271
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionThe University of Tokushima

Principal Investigator

TSUNEMATSU Takaaki  徳島大学, 大学院医歯薬学研究部(医学域), 助教 (70726752)

Research Collaborator ISHIMARU Naozumi  
KUDO Yasusei  
ARAKAKI Rieko  
KAWAI Hidehiko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
KeywordsDNA複製 / ユビキチン / タンパク分解 / siRNAライブラリー / 実験腫瘍学 / siRNAライブラリ
Outline of Final Research Achievements

DNA replication is restricted to occur once per cell cycle and its deregulation cause excessive chromosomal numbers called DNA re-replication. The chromosomal abnormality is one of the hallmarks of cancer. So, the understanding of its regulation is important for analyzing cancer biology. In this study, we try to identify novel mechanisms which suppress DNA re-replication by using genome-wide siRNA library. We found that knockdown of each genes did not cause DNA re-replication besides known regulators. Finally, we identified the novel regulators of DNA re-replication by siRNA screening with DNA re-replication inducing reagent.

Academic Significance and Societal Importance of the Research Achievements

本研究で着目するDNA再複製と呼ばれる現象は染色体数の異常な増加を引き起こすことから発癌や癌の進展に関与する可能性があり、癌の生物学を理解する上で重要な生命現象と考えられる。一方で癌細胞に持続的にDNA再複製を誘導すると細胞老化を引き起こし、細胞死に至ることから、癌の治療法としても可能性を有しており、その制御機構の解明は非常に意義深いと考えられる。本研究成果によって同定した新規のDNA再複製制御機構が発癌及び癌の進展の理解、癌の治療法の開発の新たな分子基盤となりうると考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (15 results)

All 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Invasion-related factors as potential diagnostic and therapeutic targets in oral squamous cell carcinoma.2018

    • Author(s)
      Siriwardena SBSM, Tsunematsu T, Qi G, Ishimaru N, Kudo Y.
    • Journal Title

      Int J Mol Sci

      Volume: 19 Issue: 5 Pages: 1462-1462

    • DOI

      10.3390/ijms19051462

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells2018

    • Author(s)
      Utaijaratrasmi Penkhae、Vaeteewoottacharn Kulthida、Tsunematsu Takaaki、Jamjantra Pranisa、Wongkham Sopit、Pairojkul Chawalit、Khuntikeo Narong、Ishimaru Naozumi、Sirivatanauksorn Yongyut、Pongpaibul Ananya、Thuwajit Peti、Thuwajit Chanitra、Kudo Yasusei
    • Journal Title

      Molecular Cancer

      Volume: 17 Issue: 1

    • DOI

      10.1186/s12943-018-0760-x

    • NAID

      120006714441

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Aurora Kinase Inhibitors In Head And Neck Cancer.2018

    • Author(s)
      Qi G, Liu J, Mi S, Tsunematsu T, Jin S, Shao W, Liu T, Ishimaru N, Tang B, Kudo Y.
    • Journal Title

      Curr Top Med Chem.

      Volume: - Issue: 3 Pages: 199-213

    • DOI

      10.2174/1568026618666180112163741

    • NAID

      120006729373

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NF-κB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression of CXCR4 in a Mouse Model of Sjogren's Syndrome.2017

    • Author(s)
      Kurosawa M, Arakaki R, Yamada A, Tsunematsu T, Kudo Y, Sprent J, Ishimaru N.
    • Journal Title

      Arthritis Rheumatol.

      Volume: 69 Issue: 11 Pages: 2193-2202

    • DOI

      10.1002/art.40230

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene.2017

    • Author(s)
      Kujiraoka S, Tsunematsu T, Sato Y, Yoshida M, Tohyama R, Tanaka M, Kobayashi Y, Kondo T, Ushio A, Otsuka K, Kurosawa M, Saito M. Yamada A, Arakaki R, Nagai H, Nikai H, Takeuchi K, Nagao T, Miyamoto Y, Ishimaru N, Kudo Y.
    • Journal Title

      Oral Oncol.

      Volume: 69 Pages: 46-55

    • DOI

      10.1016/j.oraloncology.2017.04.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human odontogenic epithelial cells derived from epithelial rests of Malassez possess stem cell properties.2016

    • Author(s)
      Tsunematsu T, Fujiwara N, Yoshida M, Takayama Y, Kujiraoka S, Qi G, Kitagawa M, Kondo T, Yamada A, Arakaki R, Miyauchi M, Ogawa I, Abiko Y, Nikawa H, Murakami S, Takata T, Ishimaru N, Kudo Y.
    • Journal Title

      Lab Invest.

      Volume: 96(10) Issue: 10 Pages: 1063-1075

    • DOI

      10.1038/labinvest.2016.85

    • NAID

      120006718349

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oral environment and cancer.2016

    • Author(s)
      Kudo Y, Tada H, Fujiwara N, Tada Y, Tsunematsu T, Miyake Y, Ishimaru N.
    • Journal Title

      Genes Environ.

      Volume: 1 Issue: 1 Pages: 38-13

    • DOI

      10.1186/s41021-016-0042-z

    • NAID

      120006937648

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ameloblastin induces tumor suppressive phenotype and enhances chemosensitivity to doxorubicin via Src-Stat3 inactivation in osteosarcoma.2016

    • Author(s)
      Ando T, Kudo Y, Iizuka S, Tsunematsu T, Umehara H, Shrestha M, Matsuo T, Kubo T, Shimose S, Arihiro K, Ogawa I, Ochi M, Takata T.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 40187-40187

    • DOI

      10.1038/srep40187

    • NAID

      120006534974

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] DNAライセンシング因子CDT1の新規ユビキチン分解機構とその意義の解明2018

    • Author(s)
      常松貴明、工藤保誠、山田安希子、新垣理恵子、小川博久、常山幸一、石丸直澄
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] タンパク質のユビキチン分解を介した細胞周期と分化の制御機構2017

    • Author(s)
      常松 貴明, 山田 安希子, 新垣 理恵子, 石丸 直澄, 工藤 保誠
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 多能性幹細胞におけるユビキチンプロテアソーム経路による未分化性維持機構2017

    • Author(s)
      常松 貴明, 工藤 保誠, 山田 安希子, 新垣 理恵子, 石丸 直澄
    • Organizer
      第59回日本歯科基礎医学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Chromosome passenger complex protein, Borealin is regulated by APC/CCdh1 ubiquitin ligase and maintains pluripotent state in pluripotent stem cells2017

    • Author(s)
      Takaaki Tsunematsu, Naozumi Ishimaru, Yasusei Kudo
    • Organizer
      Gordon research conference 2017, cell growth and proliferation
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胎児性癌細胞におけるユビキチンプロテアソーム経路による未分化性維持機構2017

    • Author(s)
      常松 貴明, 工藤 保誠, 山田 安希子, 新垣 理恵子, 常山 幸一, 石丸 直澄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 癌の発生・進展に関する分子病理学的研究2016

    • Author(s)
      常松貴明
    • Organizer
      第105回日本病理学会総会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 染色体パッセンジャー複合体タンパク質Borealinのユビキチン分解の意義とその癌化への関与2016

    • Author(s)
      常松貴明、工藤保誠、山田安希子、新垣理恵子、小川博久、常山幸 一、石丸直澄
    • Organizer
      第105回日本病理学会総会
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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