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

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390094
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: TAKATA Minoru 京都大学, 放射線生物研究センター, 教授 (30281728)
• Co-Investigator(Kenkyū-buntansha): ITAYA Akiko 京都大学, 放射線生物研究センター, 研究員 (50535812) ; TOMIDA Junya 京都大学, 放射線生物研究センター, 研究員 (50511367)
• Project Period (FY): 2009 – 2011
• 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

Research Abstract

Faconi anemia(FA) is a hereditary disorder characterized by progressive bone marrow failure, increased incidence of cancer, and deficiency of DNA repair driven by the ubiquitin system. In this study, we have clarified a role of checkpoint kinase ATR in triggering DNA damage-induced activation of theFA DNA repair pathway. Furthermore, we have discovered that some FA proteins promote association of essential ATR interacter ATRIP to chromatin.

Research Products

• [Journal Article] DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI (2012)
  • Author(s): Sato K, Toda K, Ishiai M, Takata M, Kurumizaka H
  • Journal Title: Nucleic Acids Res
  • DOI: DOI:10.1093/nar/gks053
  • Peer Reviewed
• [Journal Article] ATR-Chkl signaling pathway and homologous recombinational repair protect cells from 5-fluorouracil cytotoxicity (2012)
  • Author(s): Fujinaka Y, Matsuoka K, Iimori M, Tuul M, Sakasai R, Yoshinaga K, Saeki H, Morita M, Kakeji Y, Gillespie DA, Yamamoto KI, Takata M, Kitao H, Maehara Y
  • Journal Title: DNA Repair Volume: 1(3) Pages: 247-58
  • DOI: DOI:10.1016/j.dnarep.2011.11.005
  • Peer Reviewed
• [Journal Article] TR-ATRIP kinase complex triggers activation of the Fanconi anemia DNA repair pathway (2012)
  • Author(s): Shigechi T, Tomida J, Sato K, Kobayashi M, Eykelenboom JK, Pessina F, Zhang Y, Uchida E, Ishiai M, Lowndes NF, Yamamoto K, Kurumizaka H, Maehara Y, Takata M
  • Journal Title: Cancer Res Volume: 72(5) Pages: 1149-56
  • DOI: DOI:10.1158/0008-5472.CAN-11-2904
  • Peer Reviewed
• [Journal Article] Formaldehyde catabolism is essential in cells deficient for the Fanconi anemia DNA-repair pathway (2011)
  • Author(s): Rosado IV, Langevin F, Crossan GP, Takata M, Patel KJ
  • Journal Title: Nat Struct Mol Biol Volume: 18(12) Pages: 1432-4
  • DOI: DOI:10.1038/nsmb.2173
  • Peer Reviewed
• [Journal Article] Predisposition to cancer caused by genetic and functional defects of Mammalian atad5 (2011)
  • Author(s): Bell DW, Sikdar N, Lee KY, Price J C, Chatterjee R, Park HD, Fox J, Ishiai M, Rudd ML, Pollock LM, Fogoros SK, Mohamed H, Hanigan CL ; NISC Comparative Sequencing Program, Zhang S, Cruz P, Renaud G, Hansen NF, Cherukuri PF, Borate B, McManus KJ, Stoepel J
  • Journal Title: PLoS Genet Volume: 7(8) Pages: e1002245
  • DOI: DOI:10.1371/journal.pgen.1002245
  • Peer Reviewed
• [Journal Article] Direct Inhibition of TNF-u Promoter Activity by Fanconi Anemia Protein FANCD2 (2011)
  • Author(s): Matsushita N, Endo Y, Sato K, Kurumizaka H, Yamashita T, Takata M, Yanagi S
  • Journal Title: PLoS One Volume: 6(8) Pages: e23324
  • DOI: DOI:10.1371/journal.pone.0023324
  • Peer Reviewed
• [Journal Article] The role of SNM1 family nucleases in etoposide-induced apoptosis (2011)
  • Author(s): Endo Y, Abe T, Ishiai M, Takata M, Enomoto T, Seki M.
  • Journal Title: iochem Biophys Res Commun Volume: 410(3) Pages: 568-73
  • DOI: DOI:10.1016/j.bbrc.2011.06.027
  • Peer Reviewed
• [Journal Article] FancJ/Bripl helicase protects against genomic losses and gains in vertebrate cells (2011)
  • Author(s): Kitao H, Nanda I, Sugino RP, Kinomura A, Yamazoe M, Arakawa H, Schmid M, Innan H, Hiom K, Takata M
  • Journal Title: Genes to Cells Volume: 16(6) Pages: 714-27
  • DOI: DOI:10.1111/j.1365-2443.2011.01523
  • Peer Reviewed
• [Journal Article] USP1 deubiquitinase maintains phosphorylated CHK1 by limiting its DDB1-dependent degradation (2011)
  • Author(s): Guervilly JH, Renaud E, Takata M, Rosselli F
  • Journal Title: Hum Mol Genet Volume: 20(11) Pages: 2171-81
  • DOI: DOI:10.1093/hmg/ddr103
  • Peer Reviewed
• [Journal Article] The involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway (2011)
  • Author(s): Yamamoto KY, Kobayashi S, Kurumizaka H, Takata M, Kono K, Jiricny J, Takeda S, Hirota K
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108(16) Pages: 6492-6
  • DOI: DOI:10.1073/pnas.1018487108
  • Peer Reviewed
• [Journal Article] Fanconi anemia : a disorder defective in the DNA damage response (2011)
  • Author(s): Kitao H, Takata M
  • Journal Title: Int J Hematol Volume: 93(4) Pages: 417-24
  • DOI: DOI:10.1007/s12185-011-0832-9
  • Peer Reviewed
• [Journal Article] Guest editorial : fanconi anemia and the DNA damage response (2011)
  • Author(s): Takata M
  • Journal Title: Int J Hematol Volume: 93(4) Pages: 415-6
  • DOI: DOI:10.1007/s12185-011-0832-9
  • Peer Reviewed
• [Journal Article] KIAA1018/FAN1 nuclease protects cells against genomic instability induced by interstrand cross-linking agents (2010)
  • Author(s): azunori Yoshikiyo, Katja Kratz, Kouji Hirota, Kana Nishihara, Minoru Takata, Hitoshi Kurumizaka, Satoshi Horimoto, Shunichi Takeda and Josef Jiricny.
  • Journal Title: PNAS Volume: 107(50) Pages: 21553-7
  • DOI: doi:10.1073/pnas.1011081107
  • Peer Reviewed
• [Journal Article] Chemopreventive effects of gefitinib on nonsmoking-related lung tumorigenesis in activating epidermal growth factor receptor transgenic mice (2009)
  • Author(s): Ohashi K, Takigawa N, Osawa M, Ichihara E, Takeda H, Kubo T, Hirano S, Yoshino T, Takata M, Tanimoto M, Kiura K.
  • Journal Title: Cancer Res Volume: 69(17) Pages: 7088-95
  • DOI: doi:10.1158/0008-5472.CAN-08-4205
  • Peer Reviewed
• [Journal Article] The Fanconi anemia pathway : Insights from somatic cell genetics using DT40 cell line (2009)
  • Author(s): Takata M, Ishiai M, Kitao H
  • Journal Title: Invited review Mutat Res Volume: 668(1-2) Pages: 92-102
  • DOI: 10.1016/j.mrfmmm.2008.12.012
  • Peer Reviewed
• [Presentation] The Sugahara Memorial International Symposium on Prospective Topics and Charm of Radiation Biology (2012)
  • Author(s): Minoru Takata
  • Organizer: Fanconi anemia and the DNA damage response
  • Place of Presentation: Kyoto
  • Year and Date: 20120125-26
• [Presentation] DNA損傷への応答メカニズムと疾患 (2012)
  • Author(s): 高田穣
  • Organizer: 第ll回分子予防環境医学研究会シンポジウムオーガナイザー & 演者
  • Place of Presentation: 倉敷市
  • Year and Date: 2012-01-27
• [Presentation] Genome Dynamics : molecular network in maintenance and conversion:molecularnetworkinmaintenanceandconversion (2011)
  • Author(s): 高田穣
  • Organizer: 日本分子生物学会第34回年会
  • Place of Presentation: 横浜市
  • Year and Date: 20111213-16
• [Presentation] Molecular mechanisms of the Fanconi anemia pathway. (2011)
  • Author(s): Masamichi Ishiai, Junya Tomida, Tomoko Shigechi, Akiko Itaya, Emi Uchida, Junya Unno, Minoru Takata
  • Organizer: 日本分子生物学会第34回年会
  • Place of Presentation: 横浜市
  • Year and Date: 20111213-16
• [Presentation] リン酸化プロテオミクスを用いた新規DNA損傷初期応答キナーゼの探索 (2011)
  • Author(s): 足立淳、鳴海良平、佐野聖三、久家貴寿、白水崇、松本雅記、中山敬一、井倉正枝、井倉毅、高田穣、朝長毅
  • Organizer: 日本分子生物学会第34回年会
  • Place of Presentation: 横浜市
  • Year and Date: 20111213-16
• [Presentation] Mass spectrometric analysis identifiles factors associated with the Fanconi anemia proteins FANCD2 and FANCI (2011)
  • Author(s): unya Unno, Akiko Itaya, Junya Tomida, Tsuyoshi Ikura, Minoru Takata
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜市
  • Year and Date: 20111213-16
• [Presentation] Homologous recombinational repair and Chk1-mediated S-phase arrest protect cells from 5-FU cytotoxicity repair and Chkl-mediated S-phase arrest protect cells from (2011)
  • Author(s): Hiroyuki Kitao, Yoshihiko Fujinaka, Kazuaki Matsuoka, Makoto Iimori, Munkhbold Tuul, Ryo Sakasai, Ken-ichi Yamamoto, Minoru Takata, Yoshihiko Kakeji, Yoshihiko Maehara
  • Organizer: 日本分子生物学会第34回年会
  • Place of Presentation: 横浜市
  • Year and Date: 20111213-16
• [Presentation] ファンコニ貧血蛋白FANCD2によるNF-kappaB転写制御機構の解析 (2011)
  • Author(s): 松下暢子、菊間啓太、太田莉英子、もたい龍介、徳山郷±、高田穣、胡桃坂仁志、山下孝之、稲留涼子、柳茂
  • Organizer: 日本分子生物学会第34回年会
  • Place of Presentation: 横浜市
  • Year and Date: 20111213-16
• [Presentation] Histone chaperone activity of the FANCD2-FANCI complex and its importance in repair of interstrand DNA crosslinks by the Fanconi anemia pathway (2011)
  • Author(s): oichi Sato, Masamichi Ishiai, Kazue Toda, Satoshi Furukoshi, Akihisa Osakabe, Hiroaki Tachiwana, Yoshimasa Takizawa, Wataru Kagawa, Hiroyuki Kitao, Naoshi Dohmae, Chikashi Obuse, Hiroshi Kimura, Minoru Takata, Hitoshi Kurumizaka
  • Organizer: 日本分子生物学会第34回年会
  • Place of Presentation: 横浜市
  • Year and Date: 20111213-16
• [Presentation] Robust stimulation of the FANCD2 monoubiquitination by three-way brached DNAs (2011)
  • Author(s): Kazue Toda, Koichi Sato, Masamichi Ishiai, Minoru Takata, Hitoshi Kurumizaka
  • Organizer: 日本生物学会第34回年会
  • Place of Presentation: 横浜市
  • Year and Date: 20111213-16
• [Presentation] Mcm8 and Mcm9 form a novel complex involved in resistance to DNA crosslinking agents (2011)
  • Author(s): Kohei Nishimura, Masamichi Ishiai, Tatsuo Fukagawa, Minoru Takata, Haruhiko Takisawa, Masato Kanemaki
  • Organizer: 日本生物学会第34回年会
  • Place of Presentation: 横浜市
  • Year and Date: 20111213-16
• [Presentation] ATR-ATRIP kinase complex is responsible for triggering of the FA pathway (2011)
  • Author(s): Tomoko Shigechi, Junya Tomida, Koichi Sato, Masahiko Kobayashi, John Eykelenboom, Pessina Fabio, Zhang Yanbin, Emi Uchida, Masamichi Ishiai, Noel Lowndes, Kenichi Yamamoto, Hitoshi Kurumizaka, Yoshihiko Maehara, Minoru Takata
  • Organizer: 日本生物学会第34回年会
  • Place of Presentation: 横浜市
  • Year and Date: 20111213-16
• [Presentation] Fanconi anemia and the DNA damage signaling (2011)
  • Author(s): Minoru Takata
  • Organizer: 7th RBC-NIRS International Symposium
  • Place of Presentation: Kyoto
  • Year and Date: 20111209-10
• [Presentation] ファンコニ貧血蛋白質FANCD2/FANCI結合タンパク質のプロテオーム解析 (2011)
  • Author(s): 海野純也、板谷(内田)亜希子、冨田純也、井倉毅、高田穣
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸市
  • Year and Date: 20111117-19
• [Presentation] 複製ストレスによるファンコニ貧血経路の活性化には、ATR-ATRIPキナーゼ複合体が必須である (2011)
  • Author(s): 茂地智子、冨田純也、佐藤浩一、小林昌彦、内田恵美、山本健一、胡桃坂仁志、前原善彦、高田穣
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸市
  • Year and Date: 20111117-19
• [Presentation] ファンコニ貧血とDNA損傷シグナリン」ポジウム[Internationa session for DNA repair and related subjects (2011)
  • Author(s): Takata, M
  • Organizer: H放射線影響学会
  • Place of Presentation: 神戸市
  • Year and Date: 20111117-19
• [Presentation] An Absolute Requirement of ATRIP-ATR Kinase in Replication Stress-induced Triggering of the FA Pathway Activation (2011)
  • Author(s): T. Shigechi, J. Tomida, K. Sato, Y. Zhang, E. Uchida, J. Eykelenbo, N. Lowndes, H. Kurumizaka, Y. Maehara, M. Takata
  • Organizer: 23rd ANNUAL Fanconi Anemia Research Fund SCIENTIFIC SYMPOSIUM
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20111020-23
• [Presentation] Inhibition of NHEJ Reveals Distinct Roles for FANCG in the Repair of Interstrand Crosslinks and DNA Strand Breaks (2011)
  • Author(s): J. B. Wilson, J. K. Lingley, F. A. Makki, A. M. Alandwani, K. Lee, Y. Xiao, M. Takata, G. M. Kupfer, N. J. Jones
  • Organizer: 23rd ANNUAL Fanconi Anemia Research Fund SCIENTIFIC SYMPOSIUM
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20111020-23
• [Presentation] ファンコニ貧血DNA修復経路の中心タンパク質FANCD2はヌクレオソームアセンブリー活性を示す (2011)
  • Author(s): 石合正道、佐藤浩一、高田穣、胡桃坂仁志
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 20111003-05
• [Presentation] ファンコニ貧血コア複合体によるATR-ATRIPキナーゼのクロマチン動態制御 (2011)
  • Author(s): 高田穣、冨田純也、板谷(内田)亜希子、茂地智子、海野純也、前原善彦、石合正道
  • Organizer: 第70回日本癌学会学術総会シンポジウム
  • Place of Presentation: 名古屋市
  • Year and Date: 20111003-05
• [Presentation] 複製ストレスによるFA経路の活性化には、ATRIP-ATRキナーゼが必須である (2011)
  • Author(s): 茂地智子、冨田純也、佐藤浩一、海野純也、小林昌彦、山本健一、石合正道、胡桃坂仁志、前原善彦、高田穣
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 古屋市
  • Year and Date: 20111003-05
• [Presentation] Fanconi貧血原因遺伝子餌艦η2及びE郡01一の機能解析 (2011)
  • Author(s): 佐藤浩一, 石合正道, 戸田和江, 古越聡, 越坂部晃永, 立和名博昭, 堂前直, 小布施力史, 木村宏, 高田穣, 胡桃坂仁志
  • Organizer: 第9回核ダイナミクス研究会
  • Place of Presentation: 伊豆市
  • Year and Date: 20110527-29
• [Presentation] 特別企画プログラム東京ビッグサイト (2011)
  • Author(s): 高田穣
  • Organizer: 第28回日本医学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-17
• [Presentation] FANCI phosphorylation by ATR kinase proceeds in a Rad17/TopBP1-independent manner (2010)
  • Author(s): Junya Tomida, Akiko Itaya, Emi Uchida, Tomoko Shigechi, Masahiko Kobayashi, Ken-ichi Yamamoto, Masae Ikura, Tsuyoshi Ikura, Agata Smogorzewska, Masamichi Ishiai, Minoru Takata
  • Organizer: 第33回年会日本生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-09
• [Presentation] DNAダメージにおけるArtemisの核内動態制御 (2010)
  • Author(s): 石合正道、島弘季、田代聡、高田穣
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸市
  • Year and Date: 20101207-09
• [Presentation] FAAP20 is Required for Normal Activation of the Fanconi Anemia-associated DNA Damage Response Pathway (2010)
  • Author(s): Z. Yan, R. Guo, W. Shen, D. FoxIII, A. B. Oostra, M. Takata, D. Schindler, H. oatlin, J. de Winter, W. Wang.
  • Organizer: 22nd Fanconi Anemia Research Fund Scientific Symposium
  • Place of Presentation: Minnesota(USA)
  • Year and Date: 20101021-24
• [Presentation] FANCG Functions Independently of the FA Core Complex in Homologous Recombination Repair of Phleomycin-induced DNA Damage (2010)
  • Author(s): N. J. Jones, A. Aladwani, Y. Xiao, V. S. Mysore, G. M. Kupfer, M. Takata, J. B. Wilson
  • Organizer: 22nd Fanconi Anemia Research Fund Scientific Symposium
  • Place of Presentation: Minnesota(USA)
  • Year and Date: 20101021-24
• [Presentation] DNA損傷応答におけるファンコニ貧血経路の活性化メカニズム (2010)
  • Author(s): 冨田純也、板谷亜希子、内田恵美、茂地智子、井倉正枝、胡桃坂仁志、井倉毅、石合正道、高田穣
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: ワークショップ京都
  • Year and Date: 20101020-21
• [Presentation] Artemisの核内動態制御機構の解析 (2010)
  • Author(s): 石合正道、島弘季、田代聡、高田穣
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: ワークショップ京都市
  • Year and Date: 20101020-21
• [Presentation] How we can achieve disruption of the genes essential for cell viability in DT40 cells? (2010)
  • Author(s): Minoru Takata
  • Organizer: EMBO practical course
  • Place of Presentation: Ireland
  • Year and Date: 20100712-21
• [Presentation] Gene targeting : vector design and construction EMBO practical course (2010)
  • Author(s): Minoru Takata
  • Organizer: EMBO practical course
  • Year and Date: 20100612-21
• [Presentation] リン酸化・モノユビキチン化によるファンコニ貧血・DNA修復経路の活性化メカニズム (2010)
  • Author(s): 石合正道, 冨田純也, 茂地智子, 板谷亜希子, 高田穣
  • Organizer: 第9回核ダイナミクス研究会
  • Place of Presentation: 伊豆市
  • Year and Date: 20100527-29
• [Presentation] Activation mechanisms of the Fanconi anemia pathway (2010)
  • Author(s): Minoru Takata
  • Organizer: Traute Schroeder-Kurth Symposium at the University of Wu rzburg
  • Place of Presentation: Gemmany
  • Year and Date: 20100508-18
• [Presentation] 発がんとDNA損傷応答の分子メカニズム (2010)
  • Author(s): 高田穣
  • Organizer: 肺がん分子病態研究会
  • Year and Date: 2010-09-11
• [Presentation] Activation mechanisms of the Fanconi anemia pathway via ATR signaling (2010)
  • Author(s): 高田穣
  • Organizer: 放射線生物若手の会(原子炉実験所
  • Year and Date: 2010-09-10
• [Presentation] A novel role of the FA core complex in FANCI phosphorylation, an important switch in the FA pathway (2009)
  • Author(s): Minom Takata, Junva Tomida, Tomoko Shigechi, Hiroyuki Kitao, Akiko Itava, Masamichi Ishiai
  • Organizer: Twenty-first Annual Fanconi Anemia Research Fund Scientific Symposium
  • Year and Date: 20091001-04
• [Book] Evaluation of Homologous Recombinational Repair in Chicken B Lymphoma Cell Line, DT40. Methods Mol Biol (2011)
  • Author(s): Kitao H, Hirano S, Takata M
  • Total Pages: 745
• [Book] Establishment of the DNA repair-defective mutants in DT40 cells. Methods Mol Biol
  • Author(s): Ishiai M, Uchida E, and Takata M
• [Remarks]
  • URL: http://www.rbc.kyoto-u.ac.jp/Late_Effect/Site_1/Welcome.html