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Regulation of the ubiquitin system by checkpoint kinases in response to stalled replication forks

Research Project

Project/Area Number 19390087
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKyoto University

Principal Investigator

TAKATA Minoru  Kyoto University, 放射線生物研究センター, 教授 (30281728)

Co-Investigator(Kenkyū-buntansha) ISHIAI Masamichi  京都大学, 放射線生物研究センター, 准教授 (90298844)
TOMIDA Junya  京都大学, 放射線生物研究センター, 研究員 (50511367)
北尾 洋之  京都大学, 放射線生物研究センター, 研究員 (30368617)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
Fiscal Year 2008: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2007: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywordsファンコニ貧血 / チェックポイントキナーゼ / リン酸化 / モノユビキチン化 / DNA修復 / チェックポイント / ユビキチン化
Research Abstract

ファンコニ貧血は骨髄不全, 高発がん性, DNAクロスリンク修復欠損を特徴とする遺伝性疾患である. 本研究では DNA 損傷後誘導されるFANCI 蛋白質のリン酸化が, DNA 修復に重要なFANCD2 蛋白質モノユビキチン化の分子スイッチとして機能することを明らかにした. 現在, FANCI リン酸化が上流のコア複合体(ユビキチンE3 リガーゼ)の活性をいかなるメカニズムで制御するのか, 検討を進めている.

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (37 results)

All 2009 2008 2007 Other

All Journal Article (20 results) (of which Peer Reviewed: 10 results) Presentation (15 results) Book (1 results) Remarks (1 results)

  • [Journal Article] The Fanconi anemia pathway : Insights from somatic cell genetics using DT40 cell line. Invited review.2009

    • Author(s)
      Takata M, Ishiai M, Kitao H
    • Journal Title

      Mutation Research Fanconi anemia special Issue (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion2008

    • Author(s)
      Kitao H, Kimura M, Yamamoto K, Seo H, Namikoshi K, Agata Y, Ohta K, Takata M.
    • Journal Title

      Int Immunol 20(2)

      Pages: 277-84

    • NAID

      10021239538

    • Related Report
      2008 Final Research Report
  • [Journal Article] FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC32008

    • Author(s)
      Wilson JB, Yamamoto K, Marriott AS, Hussain S, Sung P, Hoatlin ME, Mathew CG, Takata M, Thompson LH, Kupfer GM, Jones NJ.
    • Journal Title

      Oncogene 27(26)

      Pages: 3641-52

    • Related Report
      2008 Final Research Report
  • [Journal Article] Induction of lung adenocarcinoma in transgenic mice expressing activated EGFR driven by the SP-C promoter2008

    • Author(s)
      Ohashi K, Rai K, Fujiwara Y, Osawa M, Hirano S, Takata K, Kondo E, Yoshino T, Takata M, Tanimoto M, Kiura K.
    • Journal Title

      Cancer Sci. 99(9)

      Pages: 1747-53

    • NAID

      10024010760

    • Related Report
      2008 Final Research Report
  • [Journal Article] KU70/80,DNA-PKcs, and Artemis are essential for the rapid induction of apoptosis after massive DSB formation2008

    • Author(s)
      Abe T, Ishiai M, Hosono Y, Yoshimura A, Tada S, Adachi N, Koyama H, Takata M, Takeda S, Enomoto T, Seki M.
    • Journal Title

      Cell Signal 20(11)

      Pages: 1978-85

    • Related Report
      2008 Final Research Report
  • [Journal Article] FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway2008

    • Author(s)
      Ishiai M, Kitao H, Smogorzewska A, Tomida J, Kinomura A, Uchida E, Saberi A, Kinoshita E, Kinoshita Kikuta E, Koike T, Tashiro S, Elledge SJ, Takata M.
    • Journal Title

      Nat Struct Mol Biol 15(11)

      Pages: 1138-46

    • Related Report
      2008 Final Research Report
  • [Journal Article] KU70/80, DNA-PKcs, and Artemis are essential for the rapidinduction of apoptosisi after massive DSB formation2008

    • Author(s)
      Abe T, et al
    • Journal Title

      Cell Signal. 20

      Pages: 1978-1985

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of radiation induced cell death in chicken B Iymphocytes by waithaferin A.2008

    • Author(s)
      Uma Devi P, Takata M, et al
    • Journal Title

      Indian J Exp Biol. 46

      Pages: 437-42

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway.2008

    • Author(s)
      Ishiai M, Kitao H, Elledge SJ, Takata M., et al
    • Journal Title

      Nat Struct Mol Biol. 15

      Pages: 1138-46

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current topics in DNA double-strand break repair.2008

    • Author(s)
      Kobayashi J, et. al.
    • Journal Title

      J Radiat Res (Tokyo) 49

      Pages: 93-103

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3.2008

    • Author(s)
      Wilson JB, et. al.
    • Journal Title

      Oncogene (epub ahead of print)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion.2008

    • Author(s)
      Kitao H, et. al.
    • Journal Title

      Int Immunology 20

      Pages: 277-84

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emergence of Epidermal Growth Factor Receptor T790M Mutation during Chronic Exposure to Gefitinib in a Non Small Cell Lung Cancer Cell Line2007

    • Author(s)
      Ogino A, Kitao H, Hirano S, Uchida A, Ishiai M, Kozuki T, Takigawa N, Takata M, Kiura K, Tanimoto M
    • Journal Title

      Cancer Res. 67(16)

      Pages: 7807-14

    • Related Report
      2008 Final Research Report
  • [Journal Article] Epidermal growth factor receptor mutation status and adjuvant chemotherapy with uracil tegafur for adenocarcinoma of the lung2007

    • Author(s)
      Suehisa H, Toyooka S, Hotta K, Uchida A, Soh J, Fujiwara Y, Matsuo K, Ouchida M, Takata M, Kiura K, Date H.
    • Journal Title

      J Clin Oncol 25(25)

      Pages: 3952-7

    • NAID

      130004903139

    • Related Report
      2008 Final Research Report
  • [Journal Article] Subcellular distribution of human RDM1 protein isoforms and their nucleolar accumulation in response to heat shock and proteotoxic stress2007

    • Author(s)
      Messaoudi L, Yang YG, Kinomura A, Stavreva DA, Yan G, Bortolin-Cavaille ML, Arakawa H, Buerstedde JM, Hainaut P, Cavaille J, Takata M, Van Dyck E.
    • Journal Title

      Nucleic Acids Res. 35(19)

      Pages: 6571-6587

    • Related Report
      2008 Final Research Report
  • [Journal Article] Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde2007

    • Author(s)
      Ridpath JR, Nakamura A, Tano K, Luke AM, Sonoda E, Arakawa H, Buerstedde JM, Gillespie DA, Sale JE, Yamazoe M, Bishop DK, Takata M, Takeda S, Watanabe M, Swenberg JA, Nakamura J.
    • Journal Title

      Cancer Res. 67(23)

      Pages: 11117-22

    • Related Report
      2008 Final Research Report
  • [Journal Article] Deubiquitination of FANCD2 Is Required for DNA Crosslink Repair2007

    • Author(s)
      Oestergaard VH, Langevin F, Kuiken HJ, Pace P, Niedzwiedz W, Simpson LJ, Ohzeki M, Takata M, Sale JE, Patel KJ.
    • Journal Title

      Mol Cell 28(5)

      Pages: 798-809

    • Related Report
      2008 Final Research Report
  • [Journal Article] Subcellular distribution of human RDM1 protein isoforms and their nucleolar accumulation in response to heat shock and proteotoxic stress2007

    • Author(s)
      Messaoudi L, et. al.
    • Journal Title

      Nucleic Acids Res 35

      Pages: 6571-6587

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deubiquitination of FANCD2 Is Required for DNA Crosslink Repair.2007

    • Author(s)
      Oestergaard VH, et. al.
    • Journal Title

      Mol Cell 28

      Pages: 798-809

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde.2007

    • Author(s)
      Ridpath JR, et. al.
    • Journal Title

      Cancer Res 67

      Pages: 11117-22

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Monoubiquitination and phosphorylation dependent activation of the Fanconi anemia pathway, Recent Development in DNA Repair Studies2009

    • Author(s)
      Minoru Takata
    • Organizer
      The 3rd International Open Laboratory Workshop
    • Place of Presentation
      放射線総合医学研究所千葉県
    • Year and Date
      2009-02-27
    • Related Report
      2008 Final Research Report
  • [Presentation] 「ファンコニ貧血経路によるゲノム安定化メカニズム」「生き物はどのようにして放射線に立ち向かうか-DNA損傷応答と適応応答-」2008

    • Author(s)
      高田穣(招待講演)
    • Organizer
      第3回放射線防護研究センターシンポジウム(放射線総合医学研究所)
    • Place of Presentation
      千葉県
    • Year and Date
      2008-12-16
    • Related Report
      2008 Final Research Report
  • [Presentation] ファンコニ貧血経路によるゲノム安定化メカニズム2008

    • Author(s)
      高田穣
    • Organizer
      第3回放射線防護研究センターシンポジウム
    • Place of Presentation
      千葉県放射線総合医学研究所
    • Year and Date
      2008-12-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] ゲノムの安定性維持メカニズムとファンコニ貧血2008

    • Author(s)
      高田穣
    • Organizer
      第101回小児血液腫瘍懇話会
    • Place of Presentation
      東京都
    • Year and Date
      2008-07-18
    • Related Report
      2008 Final Research Report
  • [Presentation] Frequent Loss of the Immunogolobulin Heavy Chain Gene Occurs in FANCJ deficient DT40 Cell Line2008

    • Author(s)
      H. Kitao, I. Nada, A. Kinomura, M. Takata
    • Organizer
      Nineteenth Annual Fanconi Anemia Research Fund Scientific Symposium
    • Place of Presentation
      Chicago
    • Related Report
      2008 Final Research Report
  • [Presentation] Role of FANCI protein and its phosphorylation for the Fanconi anemia pathway function2008

    • Author(s)
      M. Takata, H. Kitao, A. kinomura, A. Smogorzewska, S. J. Elledge, M. Ishiai
    • Organizer
      Nineteenth Annual Fanconi Anemia Research Fund Scientific Symposium
    • Place of Presentation
      Chicago
    • Related Report
      2008 Final Research Report
  • [Presentation] FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway. Symposium : "DNA repair network deficiency and carcinogenesis"2008

    • Author(s)
      Ishiai M, Kitao H, Takata M.
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋市, 神戸
    • Related Report
      2008 Final Research Report
  • [Presentation] ファンコニ貧血経路の制御とFANCI タンパク質のリン酸化メカニズム2008

    • Author(s)
      冨田純也、内田亜希子、北尾洋之、木下英司、内田恵美、小林昌彦、山本健一、小池透、石合正道、高田穣
    • 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
      神戸市
    • Related Report
      2008 Final Research Report
  • [Presentation] ファンコニ貧血経路の活性化制御とFANCIタンパク質のリン酸化メカニズム2008

    • Author(s)
      冨田純也、内田亜希子、北尾洋之、木下英司、内田恵美、小林昌彦、山本健一、小池透、石合正道、高田穣
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway Symposium.2008

    • Author(s)
      Ishiai M, Kitao H, Takata M
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋市
    • Related Report
      2008 Annual Research Report
  • [Presentation] Role of Fanci protein and its phosphorylation for the Fanconia anemia pathway function2007

    • Author(s)
      Minoru Takata
    • Organizer
      Nineteenth Annual Fanconia Anemia Research Fund Sceintific Symposium
    • Place of Presentation
      The westin Michigan Avenue, Chicago, Il, U.S.A
    • Year and Date
      2007-10-10
    • Related Report
      2007 Annual Research Report
  • [Presentation] ファンコニ貧血コア複合体によるモノユビキチン化とDNAクロスリンク修復制御2007

    • Author(s)
      高田穣、北尾洋之、木野村愛子、石合正道
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report
  • [Presentation] FancD2/FancI complex regulates crosslink repair in the Fanconi anemia pathway. "Chromosome and Genome Stability and Instability"2007

    • Author(s)
      M.Takata
    • Organizer
      Chromosome Cycle International Symposium
    • Place of Presentation
      Osaka
    • Related Report
      2008 Final Research Report
  • [Presentation] ファンコニ貧血コア複合体によるFANCD2/FANCI複合体のモノユビキチン化と相同組換え修復。ワークショップ 放射線DNA損傷修復機構研究の最前線2007

    • Author(s)
      高田穣、北尾洋之、木野村愛子、石合正道
    • Organizer
      放射線影響学会6第50回大会
    • Place of Presentation
      幕張メッセ
    • Related Report
      2008 Final Research Report
  • [Presentation] FANCJ 遺伝子欠損DT40細胞株で起こる免疫グロブリン重鎖遺伝子でのゲノム欠失2007

    • Author(s)
      北尾洋之、ナンダインドラジット、木野村愛子、シュミットマイケル、高田穣
    • Organizer
      ワークショップ第30回分子生物学会第80回日本生化学会合同大会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report
  • [Book] Fanconi anemia. A paradigmatic disease for the understanding of cancer and aging.2007

    • Author(s)
      Nanda I, et. al.
    • Total Pages
      229
    • Publisher
      Karger, Switzerland
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.rbc.kyoto-u.ac.jp/Late_Effect/Welcome%20.html

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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