Functional analysis of Fanconi anemia genes that are involved in chromosomal stability and tumor prevention

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013083
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University (2007-2009); Hiroshima University (2006); Kawasaki Medical School (2005)
• Principal Investigator: TAKATA Minoru Kyoto University, 放射線生物研究センター, 教授 (30281728)
• Co-Investigator(Kenkyū-buntansha): 松下 暢子 川崎医科大学, 医学研究科, 助手 (30333222) ; 平野 世紀 川崎医科大学, 医学研究科, 助手 (20368616) ; 北尾 洋之 京都大学, 放射線生物研究センター, 研究員 (30368617) ; 冨田 純也 京都大学, 放射線生物研究センター, 研究員 (50511367)
• Project Period (FY): 2005 – 2009
• Keywords: ファンコニ貧血 / ゲノム不安定性 / FANCD2 / FANCI / ユビキチン化

Research Abstract

Fanconi anemia is a hereditary disorder characterized by increased incidence of cancer and leukemia. FA is caused by a mutation in any one of the 14 FA genes. Their products form a nuclear biochemical network called FA pathway. We analyzed molecular function of the FA pathway by making knockout mutant cell line from chicken DT40 cells. We have partially clarified molecular details of the FA pathway and its regulatory mechanism in the DNA damage response.

Research Products

• [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., animoto M., Kiura K.
  • Journal Title: Cancer Res. 69 Pages: 7088-7095
  • Peer Reviewed
• [Journal Article] TheFanconi 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. 668 Pages: 92-102
  • 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., Smogorzewska A., Tomida J., Kinomura A., Uchida E., Saberi A., Kinoshita E., Kinoshita-Kikuta E., Koike T., Tashiro S., Elledge S.J., Takata M.
  • Journal Title: Nat. Struc. Mol. Biol. 15 Pages: 1138-1146
  • Peer Reviewed
• [Journal Article] Detection of phosphorylation on large proteins by western blotting using Phos-tag containing gel. (2008)
  • Author(s): Tomida J., Kitao H., Kinoshita E., Takata., M.
  • Journal Title: Nature Protocols 232
  • Peer Reviewed
• [Journal Article] FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2, XRCC3. (2008)
  • Author(s): Wilson J.B., Yamamoto K., Marriott A.S., Hussain S., Sung P., Hoatlin M.E., Mathew C.G., Takata M., Thompson L.H., Kupfer G.M., Jones N.J.
  • Journal Title: Oncogene 27 Pages: 3641-3652
  • Peer Reviewed
• [Journal Article] Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion. (2008)
  • Author(s): Kitao H., Kimura M., Yamamoto K., Seo H., Namikoshi K., Agata Y., Ohta K., Takata M.
  • Journal Title: Int. Immunol. 20 Pages: 277-284
  • Peer Reviewed
• [Journal Article] Deubiquitination of FANCD2 Is Required for DNA Crosslink Repair. (2007)
  • Author(s): Oestergaard V.H., Langevin F., Kuiken H.J., Pace P., Niedzwiedz W., Simpson L.J., Ohzeki M., Takata M., Sale J.E., Patel K.J.
  • Journal Title: Mol. Cell 28 Pages: 798-809
  • Peer Reviewed
• [Journal Article] in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde. (2007)
  • Author(s): Ridpath J.R., Nakamura A., Tano K., Luke A.M., Sonoda E., Arakawa H., Buerstedde J.M., Gillespie D.A., Sale J.E., Yamazoe M., Bishop D.K., Takata M., Takeda S., Watanabe M., Swenberg J.A., Nakamura J. Cells deficient
  • Journal Title: Cancer Res. 67 Pages: 11117-11122
  • Peer Reviewed
• [Journal Article] FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage response pathway. (2007)
  • Author(s): Ling C., Ishiai M., Ali A.M., Medhurst A.L., Neveling K., Kalb R., Yan Z., Xue Y., Oostra A.B., Auerbach A.D., Hoatlin M.E., Schindler D., Joenje H., de Winter J.P., Takata M., Meetei A.R., Wang W.
  • Journal Title: EMBO J. 26 Pages: 2104-2114
  • Peer Reviewed
• [Journal Article] genetic analysis of a human disease using chicken system. (2007)
  • Author(s): Takata M, Kitao H, Ishiai M. Fanconianemia
  • Journal Title: Cytogenet Genome Res. 117 Pages: 346-351
  • 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 Line. (2007)
  • Author(s): Ogino A., Kitao H., A., Ishiai M., Kozuki T., Takigawa N., Hirano S., Uchida Takata M., Kiura K., Tanimoto M.
  • Journal Title: Cancer Res. 67 Pages: 7807-7014
  • Peer Reviewed
• [Journal Article] A requirement of FancL and FancD2 monoubiquitination in DNA repair. (2007)
  • Author(s): Seki S., Ohzeki M., Uchida A., Hirano S., Matsushita N., Kitao H., Oda T., Yamashita T., Kashihara N., Tsubahara A., Takata M., Ishiai M.
  • Journal Title: Genes Cells 12 Pages: 299-310
  • Peer Reviewed
• [Journal Article] Functional interplay between BRCA2/FANCD1 and FANCC in DNA repair. (2006)
  • Author(s): Kitao H., Yamamoto K., Matsushita N., Ohzeki M., Ishiai M., Takata M.
  • Journal Title: J. Biol. Chem. 281 Pages: 21312-21320
  • Peer Reviewed
• [Journal Article] A FancD2-Monoubiquitin Fusion Reveals Hidden Functions of Fanconi Anemia Core Complex in DNA Repair. (2005)
  • Author(s): Matsushita N., Kitao H., Ishiai M., Nagashima N., Hirano S., Okawa K., Ohta T., Yu D.S., McHugh P.J., Hickson I.D., Venkitaraman A.R., Kurumizaka H., Takata M.
  • Journal Title: Mol. Cell 19 Pages: 841-847
  • Peer Reviewed
• [Presentation] DNA damage response and hematological disorder, DNA damage signaling in the Fanconi anemia pathogenesis (2009)
  • Author(s): Takata M.
  • Organizer: 第51回小児血液学会シンポジウム
  • Place of Presentation: 千葉
  • Year and Date: 20091127-20091129
• [Presentation] Regulation Of Cross-Link Repair Through The Fanconi Anemia Pathway. (2009)
  • Author(s): Takata M., Tomida J., Itaya A., Shigechi T., Ishiai M.
  • Organizer: 高松宮がん研究基金シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20091110-20091112
• [Presentation] 高発がん遺伝病ファンコニ貧血の分子メカニズム, 小児血液腫瘍の発症リスクと先天異常 (2009)
  • Author(s): 高田穣
  • Organizer: 第71回日本血液学会学術集会シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 20091023-20091025
• [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
  • Year and Date: 2008-10-29
• [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1 0 1回小児血液腫瘍懇話会
  • Place of Presentation: 東京・経団連会館
  • Year and Date: 2008-07-18
• [Presentation] Chromosome and Genome Stability and FancD2/FancI complex regulates crosslink repair in the Fanconi anemia pathway. Instability (2007)
  • Author(s): Takata M.
  • Organizer: Chromosome Cycle International Symposium
  • Place of Presentation: 大阪
  • Year and Date: 20071107-20071108
• [Presentation] Functional Pathways in Recombinational Repair. (2007)
  • Author(s): Takata M.
  • Organizer: Keystone Symposia "Genome Instability and Repair" Breckenridge
  • Place of Presentation: CO, USA.
  • Year and Date: 20070117-20070122
• [Remarks]
  • URL: http://www.rbc.kyoto-u.ac.jp/Late_Effect/Site_1/Welcome.html