Functional analysis of the FANCD2 interactors containing ubiquitin binding domain

• Project/Area Number: 23590380
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Kyoto University
• Principal Investigator: ISHIAI Masamichi 京都大学, 放射線生物研究センター, 准教授 (90298844)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ユビキチン / DNA修復 / DNA損傷応答 / ファンコニ貧血 / 癌 / 環境 / FANCD2 / DT40細胞 / UBR5 / UFD1 / タンパク質

Research Abstract

The Fanconi anemia (FA) pathway is critically involved in DNA damage responses and DNA repair. A key protein, FANCD2, is monoubiquitinated and accumulates in chromatin in response to DNA interstrand crosslinks (ICLs), where it coordinates DNA repair through mechanisms that are still poorly understand.
We have isolated UBR5 and UFD1 as candidate interacting proteins for FANCD2. Both proteins contain ubiquitin-binding domains. We have established ubr5-deficient chicken DT40 cells, and SiRNA-based ufd1-knock down human cells. Unexpectedly, ubr5-deficient or ufd1-knock down cells showed little sensitivity to ICL reagents compared to wild type cells. Laser microirradiation experiments using GFP-UBR5 or GFP-UFD1 expressing human cells showed little GFP-protein accumulation after DNA damage. These results suggested that functional relationship between FA pathway and UBR5, or UFD1 including related proteins was not strong, at least in ICL repair.

Research Products

• [Journal Article] FANCD2 Binds CtIP and Regulates DNA-End Resection during DNA Interstrand Crosslink Repair. (2014)
  • Author(s): Unno J
  • Journal Title: Cell Rep. Volume: 7 Issue: 4 Pages: 1039-1047
  • DOI: 10.1016/j.celrep.2014.04.005
  • Peer Reviewed / Open Access
• [Journal Article] Tumor suppressor RecQL5 controls recombination induced by DNA crosslinking agents (2014)
  • Author(s): Yoshifumi Hosono, Takuya Abe, Masamichi Ishiai, M. Nurul Islam, Hiroshi Arakawa, Weidong Wang, Shunichi Takeda, Yutaka Ishii, Minoru Takata, Masayuki Seki, Takemi Enomoto
  • Journal Title: Biochimica et Biophysica Acta-Molecular Cell Research Volume: 1843 Issue: 5 Pages: 1002-1012
  • DOI: 10.1016/j.bbamcr.2014.01.005
  • Peer Reviewed / Open Access
• [Journal Article] FANCD2 associated with chromatin anchors CtIP and regulates DNA end resection during DNA interstrand crosslink repair. (2014)
  • Author(s): Unno J. et. al.
  • Journal Title: Cell Report Volume: 未定
  • Peer Reviewed
• [Journal Article] A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair (2013)
  • Author(s): J Tomida, A Itaya, T Shigechi, J Unno, E Uchida, M Ikura, Y Masuda, S Matsuda J Adachi, M Kobayashi, AR Meetei, Y Maehara, K Yamamoto K Kamiya, A Matsuura, T Matsuda. T Ikura, M Ishiai, M Takata
  • Journal Title: Nucleic Acids Research Volume: VOL. 41 Issue: 14 Pages: 6930-6941
  • DOI: 10.1093/nar/gkt467
  • Peer Reviewed
• [Journal Article] Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair (2012)
  • Author(s): Koichi 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
  • Journal Title: The EMBO Journal Volume: 31 Issue: 17 Pages: 3524-3536
  • DOI: 10.1038/emboj.2012.197
  • Peer Reviewed
• [Journal Article] Mcm8 and Mcm9 form a complex that functions in homologous recombination repair induced by DNA interstrand crosslinks (2012)
  • Author(s): Nishimura, K., Ishiai, M., Hirikawa, K., Fukagawa, T., Takata, M., Takisawa, H. Kanemaki, M.T
  • Journal Title: Mol. Cell Pages: 47-47
  • Peer Reviewed
• [Journal Article] DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI (2012)
  • Author(s): Koichi Sato. Kazue Toda, Masamichi Ishiai, Minora Takata, Hitoshi Kurumizaka
  • Journal Title: Nucleic Acids Research Volume: 40 Issue: 10 Pages: 4553-4561
  • DOI: 10.1093/nar/gks053
  • Peer Reviewed
• [Journal Article] Mcm8 and Mcm9 form a complex that functions in homologous recombination induced by interstrand crosslinks (2012)
  • Author(s): K. Nishimura
  • Journal Title: Molecular Cell Volume: 47 Issue: 4 Pages: 511-522
  • DOI: 10.1016/j.molcel.2012.05.047
  • Peer Reviewed
• [Journal Article] Establishment of the DNA repair-defective mutants in DT40 cells. (2012)
  • Author(s): Ishiai M, Uchida E, Takata M.
  • Journal Title: Methods Mol Biol. Volume: 920 Pages: 39-49
  • DOI: 10.1007/978-1-61779-998-3_4
  • NAID: 120004996387
  • ISBN: 9781617799976, 9781617799983
  • Peer Reviewed
• [Journal Article] ATR-ATRIP Kinase Complex Triggers Activation of the Fanconi Anemia DNA Repair Pathway (2012)
  • Author(s): Tomoko Shigechi, Junya Tomida, Koichi Sato, Masahiko Kobayashi, John K.Eykelenboom, Fabio Pessina, Yanbin Zhang, Emi Uchida, Masamichi Ishiai, Noel F.Lowndes, Kenichi Yamamoto, Hitoshi Kurumizaka, Yoshihiko Maehara, Minoru Takata
  • Journal Title: Cancer Research Volume: 72 Issue: 5 Pages: 1149-1156
  • DOI: 10.1158/0008-5472.can-11-2904
  • Peer Reviewed
• [Journal Article] CIN85 drives B cell responses by linking BCR signals to the canonical NF-κB pathway (2011)
  • Author(s): Kometani, K., Yamada, T., Sasaki, Y., Yokosuka, T., Saito, T., Rajewsky, K., Ishiai, M., Hikida, M. and Kurosaki, T
  • Journal Title: J. Exp. Med Volume: 208 Issue: 7 Pages: 1447-1457
  • DOI: 10.1084/jem.20102665
  • Peer Reviewed
• [Journal Article] The role of SNM1 family nucleases in etoposide-induced apoptosis (2011)
  • Author(s): Hosono, Y., Abe, T., Ishiai, M., Takata, M., Enomoto, T., Seki, M.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 410 Issue: 3 Pages: 568-573
  • DOI: 10.1016/j.bbrc.2011.06.027
  • 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) Issue: 8 Pages: e1002245-e1002245
  • DOI: 10.1371/journal.pgen.1002245
  • Peer Reviewed
• [Presentation] Roles of the Fanconi anemia protein FANCD2 in DNA crosslink repair. (2014)
  • Author(s): Ishiai M, Unno J, Sato K, Itaya A, Tomida J, Kurumizaka H, Takata M.
  • Organizer: International Conference, Kyoto, 2014, “Replication, repair and transcription; coupling mechanisms and chromatin dynamics for genome integrity”
  • Place of Presentation: 京都市
• [Presentation] ファンコニ貧血原因遺伝子産物FANCD2の示すヒストンシャペロン活性の生理的意義 (2013)
  • Author(s): 石合正道, 佐藤浩一, 胡桃坂仁志, 高田穣
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] ファンコニ貧血原因遺伝子産物 FANCD2 の示すヒストンシャペロン活性の生理的意義 (2013)
  • Author(s): 石合正道、佐藤浩一、胡桃坂仁志、高田穣
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸市
  • Invited
• [Presentation] ワークショップ「DNA損傷のセンシングと分子応答の最前線」序論、および まとめ (2013)
  • Author(s): 石合正道、中村麻子
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森市
  • Invited
• [Presentation] Roles of the Fanconi anemia protein FANCD2 in DNA crosslink repair. (2013)
  • Author(s): Ishiai M, Unno J, Sato K, Itaya A, Tomida J, Kurumizaka H, Takata M. Masamichi Ishiai, Junya Unno, Koichi Sato, Akiko Itaya, Junya Tomida, Hitoshi Kurumizaka, Minoru Takata.
  • Organizer: 29th RBC-NIRS International Symposium “Next Generation” Radiation Biology and beyond: New perspectives on genome damage and stability.
  • Place of Presentation: 京都市
• [Presentation] 高発がん性疾患ファンコニ貧血原因遺伝子産物FANCD2の示すヒストンシャペロン活性の生理的意義 (2013)
  • Author(s): 石合正道
  • Organizer: 平成24年度文部科学省新学術領域「がん研究分野の特性等を踏まえた支援活動」公開シンポジウム
  • Place of Presentation: 学術総合センター 一橋講堂（東京都）
• [Presentation] ファンコニ貧血経路の示すヌクレオソーム形成活性のDNA修復における役割 (2012)
  • Author(s): 石合正道, 佐藤浩一, 高田穣, 胡桃坂仁志
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 仙台市
  • Invited
• [Presentation] Histone chaperon activity of FANCD2 Plays a crucial role in DNA crosslink repair (2012)
  • Author(s): Ishiai, M.,Sato, K., Toda, K., Furukoshi, S., Osakabe, A., Tachiwara, H., Takizawa, Y., Kagawa, W., Kitao, H., Dohmae, N., Obuse, C., Kimura H., Takata, M., Kurumizaka H
  • Organizer: Abcam International meeting on"Maintenance of Genome Stability 2012"
  • Place of Presentation: ナッソー市(バハマ国)
• [Presentation] ファンコニ貧血経路の示すヌクレオソーム形成活性のDNA修復における役割． (2012)
  • Author(s): 石合正道、佐藤浩一、髙田穣、胡桃坂仁志
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 東北大学川内北キャンパス（仙台市）
  • Invited
• [Presentation] Histone chaperon activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair. (2012)
  • Author(s): Ishiai M, Sato K, Toda K, Furukoshi S, Osakabe A, Tachiwana H, Takizawa Y, kagawa W, Kitao H, Dohmae N, Obuse C, Kimura H, Takata M and Kurumizaka H
  • Organizer: The 8th 3R symposium
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県淡路市）
• [Presentation] FANCD2のヒストンシャペロン活性がDNA修復機能に果たす役割． (2012)
  • Author(s): 石合正道、佐藤浩一、髙田穣、胡桃坂仁志
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場（福岡市）
• [Presentation] FANCD2の示すヌクレオソーム・アセンブリー活性 (2012)
  • Author(s): 石合 正道
  • Organizer: 国立遺伝学研究所 研究集会「ユビキチン・SUMOによるDNA複製およびDNA修復系の制御」(招待講演)
  • Place of Presentation: 国立遺伝学研究所 (静岡県)
• [Presentation] Histone chaperon activity of FANCD2 plays a crucial role in DNA crosslink repair (2012)
  • Author(s): Ishiai M., Sato K., Toda K., Furukoshi S., Osakabe A. Tachikawa H., Takizawa Y., Kagawa W., Kitao H., Dohmae N., Obuse C., Kimura H., Takata M. and Kurumizaka H.
  • Organizer: Abcam international meeting on "Maintenance of Genome Stability 2012"
  • Place of Presentation: ナッソー (バハマ)
• [Presentation] Molecular mechanisms of the Fanconi anemia pathway (2011)
  • Author(s): 石合正道, 冨田純也, 茂地智子, 板谷亜希子, 内田恵美, 海野純也, 高田穣
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Invited
• [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 日本癌学会学術大会
  • Place of Presentation: 名古屋国際会議場 (愛知県)
• [Presentation] Molecular mechanisms of the Fanconi anemia pathway (2011)
  • Author(s): 石合正道、冨田純也、茂地智子、板谷亜希子、内田恵美、海野純也、高田穣
  • Organizer: 第34回 日本分子生物学会年会(招待講演)
  • Place of Presentation: パシフィコ横浜 (神奈川県)
• [Book] Establishiment of the DNA repair-defective mutants in DT40 cells in"DNA repair Protocols, Methods in Molecular Biology, vol. 920 (Bjerbak ed.)"(Chapter 4) (2012)
  • Author(s): Ishiai, M., Uchida, E., Takata, M.
  • Publisher: Humana Press
• [Remarks]
  • URL: http://house.rbc.kyoto-u.ac.jp/late-effect
• [Remarks] http://house.rbc.kyoto-u.ac.jp/late-effect
• [Remarks] 京都大学放射線生物研究センター晩発効果研究部門DNA損傷シグナル研究分野
  • URL: http://house.rbc.kyoto-u.ac.jp/Late_Effect/Japanese_site/Welcome.html
• [Remarks]
  • URL: http://www.rbc.kyoto-u.ac.jp/