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New understanding and therapeutics of hematopoietic diseases-from a viewpoint of regulatory mechanisms of replicative stress

Research Project

Project/Area Number 20591109
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionGunma University

Principal Investigator

YAMASHITA Takayuki  Gunma University, 生体調節研究所, 教授 (10166671)

Co-Investigator(Kenkyū-buntansha) ODA Tsukasa  群馬大学, 生体調節研究所, 助教 (10323643)
SEKIMOTO Takayuki  群馬大学, 生体調節研究所, 助教 (20436322)
大江 良秀  群馬大学, 生体調節研究所, 助教 (80125830)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsDNA複製 / 損傷乗越えDNA合成 / Yファミリー・ポリメラーゼ / Hsp90 / 造血不全 / 複製ストレス / ファンコニ貧血 / Yファミリーポリメラーゼ / 損傷乗り越えDNA合成 / DNAポリメラーゼη / モノユビキチン化PCNA / DNA損傷 / 突然変異 / 分子シャペロン
Research Abstract

Fanconi anemia (FA) is genetically heterogeneous inherited bone marrow failure syndrome, characterized by cellular sensitivity to DNA crosslinkers and susceptibility to various types of malignant tumors including acute myeloid leukemia. Increasing evidence indicates that FA proteins protect against "replicative stress" induced by various genotoxic agents, cooperating with other machineries. Translesion DNA synthesis is one of such cellular protective mechanisms, using specialized DNA polymerases including Pol-eta and REV1.However, regulatory mechanism of these polymerases was largely unknown. We identified the molecular chaperone Hsp90 as an essential regulator of these polymerases. The present findings may lead to development of new therapy of hematopoietic diseases.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (26 results)

All 2011 2010 2009 2008 Other

All Journal Article (8 results) (of which Peer Reviewed: 5 results) Presentation (12 results) Book (2 results) Remarks (4 results)

  • [Journal Article] The Molecular Chaperone Hsp90 Regulates Accumulation of DNA Polymerase η at Replication Stalling Sites in UV-irradiated Cells.2010

    • Author(s)
      Sekimoto T, Oda T, Yamashita T., et al.
    • Journal Title

      Mol Cell 37

      Pages: 79-89

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The molecular chaperone Hsp90 regulates accumulation of DNA polymerase eta at replication stalling sites in UV-irradiated cells2010

    • Author(s)
      Sekimoto T, Yamashita T, et al.
    • Journal Title

      Molecular Cell

      Volume: 37 Pages: 79-89

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Molecular chaperone Hsp90 regulates accumulation of DNA polymerase η at replication stalling sites in UV-irradiated cells2010

    • Author(s)
      Sekimoto T, Yamashita T, et al.
    • Journal Title

      Molecular Cell 37

      Pages: 79-89

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correction of mutant Fanconi anemia gene by homologous recombination in human hematopoietic cells using adenoassociated virus vector.2009

    • Author(s)
      Paiboonsukwong K, Yamashita T, et al.
    • Journal Title

      J.Gene Med. 11

      Pages: 1012-1019

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fanconi貧血の分子病態-最近の進歩2009

    • Author(s)
      山下孝之、小田司、関本隆本
    • Journal Title

      臨床血液 50

      Pages: 538-546

    • NAID

      130004501341

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fanconi貧血の分子病態2009

    • Author(s)
      山下孝之
    • Journal Title

      分子細胞治療 8

      Pages: 89-92

    • Related Report
      2009 Annual Research Report 2008 Annual Research Report
  • [Journal Article] Fanconi貧血2009

    • Author(s)
      山下孝之、小田司、関本隆志
    • Journal Title

      臨床血液 50(印刷中)

    • NAID

      130007659587

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Fanconi貧血-ゲノム損傷ストレスと造血幹細胞の老化-2008

    • Author(s)
      山下孝之、小田司、関本隆志
    • Journal Title

      日本臨床 66

      Pages: 477-482

    • Related Report
      2008 Annual Research Report
  • [Presentation] Acute depletion of Heat shock factor (HSF) 1 triggers cell senescence program by activating multiple tumor suppressor pathways.2010

    • Author(s)
      小田司、山下孝之, ら
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] 「がんシャペロン」Hsp90はDNAポリメラーゼ-&etaによる損傷乗り越えDNA合成を促進する2010

    • Author(s)
      山下孝之
    • Organizer
      第69回 日本癌学会学術総会
    • Place of Presentation
      大阪(招待講演)
    • Year and Date
      2010-09-22
    • Related Report
      2010 Final Research Report
  • [Presentation] Acute depletion of Heat shock factor (HSF) 1 activates tumor-suppressive cell senescence program.2010

    • Author(s)
      小田司, 関本隆志, 山下孝之
    • Organizer
      第69回 日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Final Research Report
  • [Presentation] The"cancer chaperone"Hsp90 promotes DNA polymarase-eta-mediated translesion synthesis2010

    • Author(s)
      山下孝之
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 分子シャペロンHsp90はY-family DNAポリメラーゼREV1のDNA損傷による核内フォーカス形成を促進する2009

    • Author(s)
      Mayca Pozo Franklin, 小田司、関本隆志、山下孝之,ら
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-10
    • Related Report
      2010 Final Research Report
  • [Presentation] 熱ショック応答転写因子Heat shock factor 1の発現抑制はhTERT不死化ヒト細胞においてp53-p21を介する細胞老化を引き起こす2009

    • Author(s)
      小田司、関本隆志、山下孝之,ら
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] 熱ショック応答転写因子Heat shock factor 1(HSF1)の発現抑制はhTERT不死化ヒト細胞においてp53-p21を介する細胞老化を引き起こす2009

    • Author(s)
      小田司、山下孝之, ら
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] 分子シャペロンHsp90はY-family DNA Polymerase REV1のDNA損傷による核内フォーカス形成を促進する2009

    • Author(s)
      Franklin Mayca Pozo、山下孝之, ら
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] 分子シャペロンHSP90はPolymerase-η(Pol-η〉の複製フォーカスへの集積と損傷乗越えDNA合成(TLS)を促進するえDNA合成(TLS)を促進する2008

    • Author(s)
      関本隆志、小田司、フランクリン マイカ ポゾ、村雲芳樹、益谷来豪、花岡文雄、山下孝之
    • Organizer
      第31回日本分子生物学会年会第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-12
    • Related Report
      2008 Annual Research Report
  • [Presentation] 分子シャペロンHSP90はPolymerase-η(Pol-η)の複製フォーカスへの集積と損傷乗越えDNA合成(TLS)を促進する2008

    • Author(s)
      関本隆志、小田司、山下孝之,ら
    • Organizer
      第31回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-11
    • Related Report
      2010 Final Research Report
  • [Presentation] Fanconi貧血の分子病態-最近の進歩2008

    • Author(s)
      山下孝之、小田司、関本隆志
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都(招待講演)
    • Year and Date
      2008-10-11
    • Related Report
      2010 Final Research Report
  • [Presentation] Fanconi貧血の分子病態-最近の進歩2008

    • Author(s)
      山下孝之、小田司、関本隆志
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-11
    • Related Report
      2008 Annual Research Report
  • [Book] Annual Review血液(分担執筆)II-3 Fanconi貧血の分子病態2011

    • Author(s)
      山下孝之
    • Total Pages
      5
    • Publisher
      中外医学社
    • Related Report
      2010 Annual Research Report
  • [Book] Annual Review血液2011(Fanconi貧血の分子病態)

    • Author(s)
      山下孝之
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ

    • URL

      http://www.imcr.gunma-u.ac.jp/lab/molgen/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.imcr.gunma-u.ac.jp/lab/molgen/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.imcr.gunma-u.ac.jp/gcoe/jpn/achievements/index.html

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.imcr.gunma-u.ac.jp/lab/molgen/

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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