Structure-function relationships of Rad51-Swi5-Sfr1 complex for homologous recombination

• Project/Area Number: 23770105
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: High Energy Accelerator Research Organization (2012); The University of Tokyo (2011)
• Principal Investigator: KUWABARA Naoyuki 大学共同利用機関法人高エネルギー加速器研究機構, 物質構造科学研究所, 研究員 (70506253)
• Research Collaborator: SATO Mamoru 横浜市立大学, 大学院・生命ナノシステム科学研究科, 教授 (60170784) ; IKEGUCHI Mitsunori 横浜市立大学, 大学院・生命ナノシステム科学研究科, 准教授 (60261955) ; IWASAKI Hiroshi 東京工業大学, 大学院・生命理工学研究科, 教授 (60232659) ; SHIMIZU Toshiyuki 東京大学, 大学院・薬学系研究科, 教授 (30273858)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 相同組換え / DNA 修復 / メディエーター / DNA修復

Research Abstract

In this study, I made focus on the structure-function relationships of Swi5-Sfr1 complex that interacts Rad51. I revealed the complex structure of Swi5 and C-terminal region of Sfr1 by X-ray crystallography and found that this protein complex is essential for Rad51 activation. Furthermore, we showed that Swi5-Sfr1 complex enters the groove of Rad51 filament in the activation process, and intrinsically disorder regions of Sfr1 is important in the process. From these results, I proposed a model of Rad51 activating mechanism by Swi5-Sfr1.

Research Products

• [Journal Article] Structural basis for vitamin D receptor agonism by novel non-secosteroidal ligands (2013)
  • Author(s): Lisa Asano, Ichiaki Ito, Naoyuki Kuwabara, Tsuyoshi Waku, Junn Yanagisawa, Hiroyuki Miyachi, Toshiyuki Shimizu
  • Journal Title: FEBS lettters Volume: 587 Issue: 7 Pages: 957-963
  • DOI: 10.1016/j.febslet.2013.02.028
  • Peer Reviewed
• [Journal Article] Characterisation of an intrinsically disordered protein complex of Swi5-Sfr1 by ion mobility mass spectrometry and small-angle X-ray scattering (2013)
  • Author(s): Saikusa K, Kuwabara N, Kokabu Y, Inoue Y, Sato M, Iwasaki H, Shimizu T, Ikeguchi M, Akashi S
  • Journal Title: Analys Volume: 138 Issue: 5 Pages: 1441-14499
  • DOI: 10.1039/c2an35878f
  • NAID: 120006557136
  • Peer Reviewed
• [Journal Article] Mechanistic insights into the activation of Rad51-mediated strand exchange from the structure of a recombination activator, the Swi5-Sfr1 complex (2013)
  • Author(s): N.Kuwabara, Y.Murayama, H.Hashimoto, Y.Kokabu, M.Ikeguchi, M.Sato, K.Mayanagi, Y.Tsutsui, H.Iwasaki,and T.Shimizu
  • Journal Title: Structure Volume: 20 Issue: 3 Pages: 440-449
  • DOI: 10.1016/j.str.2012.01.005
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator-activated receptors (PPARs) have multiple binding points (2012)
  • Author(s): Kuwabara N, Oyama T, Tomioka D, Ohashi M, Yanagisawa J, Shimizu T, Miyachi H.
  • Journal Title: J. Med.Chem. Volume: 55 Issue: 2 Pages: 893-902
  • DOI: 10.1021/jm2014293
  • Peer Reviewed
• [Journal Article] Fission yeast Swi5-Sfr1 protein complex, an activator of Rad51 recombinase, forms an extremely elongated dogleg-shaped structure (2011)
  • Author(s): Kokabu Y, Murayama Y, Kuwabara N, Oroguchi T, Hashimoto H, Tsutsui Y, Nozaki N, Akashi S, Unzai S, Shimizu T, Iwasaki H, Sato M, Ikeguchi M
  • Journal Title: J Biol Chem Volume: 286 Issue: 50 Pages: 43569-43576
  • DOI: 10.1074/jbc.m111.303339
  • Peer Reviewed
• [Presentation] Structural basis of the broad carbohydrates specificity of a fungal galectin from Agrocybe cylindricea (2013)
  • Author(s): Naoyuki Kuwabara, Dan Hu, Jun Hirabayashi, Ryuichi Kato
  • Organizer: 物構研サイエンスフェスタ
  • Place of Presentation: 茨城県
  • Year and Date: 2013-03-14
• [Presentation] Structural basis of the broad carbohydrates specificity of a fungal galectin from Agrocybe cylindricea (2013)
  • Author(s): Naoyuki Kuwabara, Dan Hu, Jun Hirabayashi, Ryuichi Kato
  • Organizer: 物構研サイエンスフェスタ
  • Place of Presentation: つくば国際会議場エポカル
• [Presentation] Structural basis for vitamin D receptor agonism by novel nonsecosteroidal ligands (2012)
  • Author(s): Lisa Asano, Ichiaki Ito, Naoyuki Kuwabara, Junn Yanagisawa, Hiroyuki Miyachi, Toshiyuki Shimizu
  • Organizer: AsCA 12
  • Place of Presentation: オーストラリア アデレード
• [Presentation] Circular and Linear Dichroism analyses of Swi5/Sfr1/Rad51 complex (2011)
  • Author(s): Naoyuki Kuwabara
  • Organizer: New frontier of the research in Rad51 recombinase and its accessory proteins
  • Place of Presentation: フランス パリ
  • Year and Date: 2011-09-28
• [Presentation] Structural analysis of Swi5-Sfr1 complex, mediators for homologous recombination (2011)
  • Author(s): Naoyuki Kuwabara, Hiroshi Hashimoto, Yuichi Kokabu, Mitsunori Ikeguchi, Mamoru Sato, Kouta Mayanagi, Yasuto Murayama, Hiroshi Iwasaki, Toshiyuki Shimizu
  • Organizer: 第11回日本蛋白質科学会年会
  • Place of Presentation: 大阪府
  • Year and Date: 2011-06-08
• [Presentation] Circular and Linear Dichroism analyses of Swi5/Sfr1/Rad51 complex (2011)
  • Author(s): N. Kuwabara
  • Organizer: New frontier of the research in Rad51 recombinase and its accessory proteins
  • Place of Presentation: フランス、IBPC
• [Presentation] Strucutual analysis of Swi5-Sfr1 complex, mediators for homologous recombination. (2011)
  • Author(s): N. Kuwabara, H. Hashimoto, Y. Kokabu, M. Ikeguchi, M. Sato, K. Mayanagi, Y. Murayama, H. Iwasaki, T. Shimizu
  • Organizer: 第１１回日本蛋白質科 学会年会
  • Place of Presentation: 大阪