Molecular mechanisms of DNA homology search involving nucleosomes

• Project/Area Number: 24570138
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Meisei University
• Principal Investigator: KAGAWA Wataru 明星大学, 理工学部, 准教授 (70415123)
• Co-Investigator(Renkei-kenkyūsha): KURUMIZAKA Hitoshi 早稲田大学, 先進理工学部, 教授 (80300870)
• Research Collaborator: SAOTOME Mika 明星大学, 理工学部
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 相同組換え / クロマチン / タンパク質-核酸相互作用 / ヌクレオソーム / ヒストン / 相同的対合

Outline of Final Research Achievements

The aim of this research is to understand the molecular mechanisms involved in homologous recombination in the context of the chromatin structure. Homologous recombination is initiated by a double-strand break, and is followed by the search for homologous DNA sequences in the genome. The genomic DNA, however, is composed of nucleosomes, which compacts the DNA. This compaction is a potential barrier for homologous recombination. Through structural studies of the interactions between proteins involved in promoting homologous recombination and nucleosomes, we have identified interactions between recombination proteins and nucleosomes that may provide important insights into the mechanism of DNA homology search that takes place on the chromatin.

Research Products

• [Journal Article] 出芽酵母Rad52の相同組換えにおける分子メカニズム (2014)
  • Author(s): 新井直人、香川亘
  • Journal Title: 生化学 Volume: 86 Pages: 693-697
  • NAID: 40020254551
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Crystal structure and stable property of the cancer-associated heterotypic nucleosome containing CENP-A and H3.3. (2014)
  • Author(s): Arimura Y, Shirayama K, Horikoshi N, Fujita R, Taguchi H, Kagawa W, Fukagawa T, Almouzni G, Kurumizaka H.
  • Journal Title: Sci Rep. Volume: 4 Issue: 1 Pages: 7115-7115
  • DOI: 10.1038/srep07115
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Functional analyses of the C terminal half of the Saccharomyces cerevisiae Rad52 protein (2014)
  • Author(s): Kagawa, W., Arai, N., Ichikawa, Y., Saito, K., Sugiyama, S., Saotome, M., Shibata, T. and Kurumizaka, H.
  • Journal Title: Nucleic Acids Res Volume: 42 Issue: 2 Pages: 941-951
  • DOI: 10.1093/nar/gkt986
  • Peer Reviewed
• [Journal Article] Structural polymorphism in the L1 loop regions of human H2A. Z. 1 and H2A. Z. 2. (2013)
  • Author(s): Naoki Horikoshi, Koichi Sato, Keisuke Shimada, Yasuhiro Arimura, Akihisa Osakabe, Hiroaki Tachiwana, Yoko Hayashi-Takanaka, Wakana Iwasaki, Wataru Kagawa, Masahiko Harata, Hiroshi Kimura and Hitoshi Kurumizaka.
  • Journal Title: Acta Crystallographica Section D Volume: 69 Issue: 12 Pages: 2431-2439
  • DOI: 10.1107/s090744491302252x
  • Peer Reviewed
• [Journal Article] Contribution of histone N-terminal tails to the structure and stability of nucleosomes. (2013)
  • Author(s): Wakana Iwasaki, Yuta Miya, Naoki Horikoshi, Akihisa Osakabe, Hiroyuki Taguchi, Hiroaki Tachiwana, Takehiko Shibata, Wataru Kagawa and Hitoshi Kurumizaka.
  • Journal Title: FEBS Open Bio Volume: 3 Issue: 1 Pages: 363-369
  • DOI: 10.1016/j.fob.2013.08.007
  • Peer Reviewed
• [Journal Article] Crystallization and preliminary X-ray diffraction analysis of the secreted protein Athe_0614 from Caldicellulosiruptor bescii (2013)
  • Author(s): Hiroshi Yokoyama, takahiro Yamashita, Naoki Horikoshi, Hitoshi Kurumizaka, Wataru Kagawa.
  • Journal Title: Acta Crystallographica Section F Volume: 69 Issue: 4 Pages: 438-440
  • DOI: 10.1107/s174430911300554x
  • Peer Reviewed
• [Journal Article] Purification and characterization of the fission yeast telomere clustering factors, Bqt1 and Bqt2 (2013)
  • Author(s): Ichikawa Y, Kagawa W, Saito K, C hikashige Y, Haraguchi T, Hiraoka Y , Kurumizaka H.
  • Journal Title: Protein Expr Puff. Volume: 88 Issue: 2 Pages: 207-213
  • DOI: 10.1016/j.pep.2013.01.006
  • Peer Reviewed
• [Journal Article] Current progress on structural studies of nucleosomes containing histone H3 variants (2012)
  • Author(s): Hitoshi Kurumizaka, Naoki Horikoshi, Hiroaki Tachiwana, Wataru Kagawa.
  • Journal Title: Current Opinion Structural Biology Volume: 23 Issue: 1 Pages: 109-115
  • DOI: 10.1016/j.sbi.2012.10.009
  • 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
• [Presentation] ヒトRad52タンパク質における二つのDNA結合部位の役割 (2014)
  • Author(s): 香川 亘、五月女 美香、齋藤 健吾、安田 武嗣、荻 朋男、胡桃坂 仁志
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25
• [Presentation] DNA修復タンパク質Rad52と一本鎖DNAとの複合体のX線結晶構造解析 (2014)
  • Author(s): 五月女 美香、胡桃坂 仁志、香川 亘
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25
• [Presentation] 酵母Rad52 C末端側領域の相同組換えにおける役割 (2013)
  • Author(s): 香川亘、新井直人、市川雄一、五月女美香、柴田武彦、胡桃坂仁志
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] DNA修復タンパク質Rad52と一本鎖DNAの複合体のX線結晶構造解析 (2012)
  • Author(s): 香川亘、齋藤健吾、小野寺圭一、胡桃坂仁志
  • Organizer: 第35回分子生物学会年会
  • Place of Presentation: 福岡
  • Invited