The homologous recombination reaction in chromatin

• Project/Area Number: 26890023
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Genome biology
• Research Institution: Waseda University
• Principal Investigator: Machida Shinichi 早稲田大学, 理工学術院, 助教 (50732195)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: クロマチン / 相同組換え / リンカーヒストン / ヒストン修飾 / RAD51 / RAD54 / ヒストン / ユビキチン

Outline of Final Research Achievements

Homologous recombination functions in mitotic DNA double-strand break repair and meiotic genetic recombination. In eukaryotic nucleus, homologous recombination occurs in higher ordered chromatin. However, how the chromatin architecture involved in homologous recombination reaction has not been elucidated. In this study, we revealed that the testis-specific H1 variant H1T forms
less compacted chromatin and weakly inhibited the homologous recombination reaction as compared to the representative H1 variant. In addition, we clarify how the mono-ubiquitination of histone, which is required for DNA double-strand break repair, regulates the chromatin structure.

Research Products

• [Journal Article] Chromatin architecture may dictate the target site for DMC1, but not for RAD51, during homologous pairing (2016)
  • Author(s): Kobayashi, W., Takaku, M., Machida, S., Tachiwana, H., Maehara, K., Ohkawa, Y., and Kurumizaka, H.
  • Journal Title: Scientific Reports Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Structure and function of human histone H3.Y nucleosome. (2016)
  • Author(s): Kujirai, T., Horikoshi, N., Sato, K., Maehara, K., Machida, S., Osakabe, A., Kimura, H., Ohkawa, Y. and Kurumizaka, H.
  • Journal Title: Nucleic Acids Research Volume: 1 Issue: 13 Pages: 1-15
  • DOI: 10.1093/nar/gkw202
  • Peer Reviewed / Open Access
• [Journal Article] GATA3-dependent cellular reprogramming requires activation-domain dependent recruitment of a chromatin remodeler. (2016)
  • Author(s): Takaku M, Grimm SA, Shimbo T, Perera L, Menafra R, Stunnenberg HG, Archer TK, Machida S, Kurumizaka H, Wade P.
  • Journal Title: Genome Biol. Volume: 17 Issue: 1 Pages: 36-36
  • DOI: 10.1186/s13059-016-0897-0
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Relaxed Chromatin Formation and Weak Suppression of Homologous Pairing by the Testis-Specific Linker Histone H1T. (2016)
  • Author(s): Machida S, Hayashida R, Takaku M, Fukuto A, Sun J, Kinomura A, Tashiro S, Kurumizaka H.
  • Journal Title: Biochemistry. Volume: 55 Issue: 4 Pages: 637-646
  • DOI: 10.1021/acs.biochem.5b01126
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Bivalent interaction of the PZP domain of BRPF1 with the nucleosome impacts chromatin dynamics and acetylation. (2016)
  • Author(s): Klein BJ, Muthurajan UM, Lalonde ME, Gibson MD, Andrews FH, Hepler M, Machida S, Yan K, Kurumizaka H, Poirier MG, Cote J, Luger K, Kutateladze TG.
  • Journal Title: Nucleic Acids Res. Volume: 44 Issue: 1 Pages: 472-484
  • DOI: 10.1093/nar/gkv1321
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] N-terminal phosphorylation of HP1α increases its nucleosome-binding specificity. (2014)
  • Author(s): Nishibuchi G, Machida S, Osakabe A, Murakoshi H, Hiragami-Hamada K, Nakagawa R, Fischle W, Nishimura Y, Kurumizaka H, Tagami H, Nakayama JI.
  • Journal Title: Nucleic Acids Res. Volume: 42 Issue: 20 Pages: 12498-12511
  • DOI: 10.1093/nar/gku995
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Green fluorescent protein fused to the C terminus of RAD51 specifically interferes with secondary DNA binding by the RAD51-ssDNA complex (2014)
  • Author(s): Kobayashi, W., Sekine, S., Machida, S., and Kurumizaka, H.
  • Journal Title: Genes & Genetic Systems Volume: 89 Issue: 4 Pages: 169-179
  • DOI: 10.1266/ggs.89.169
  • NAID: 130004750050
  • ISSN: 1341-7568, 1880-5779
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] The biochemical analyses of the chromatin containing mono-ubiquitinated nucleosomes (2015)
  • Author(s): Shinichi Machida, Yuki Nishiyama and Hitoshi Kurumizaka
  • Organizer: International Symposium on Chromatin Structure, Dynamics,and Function
  • Place of Presentation: 淡路島
  • Year and Date: 2015-08-23
• [Presentation] Nap1 is required for the homologous recombination reaction in higher-order chromatin containing histone H1. (2014)
  • Author(s): Machida S., Takaku M., Ikura M., Sun J., Suzuki H., Kobayashi W., Kinomura A., Osakabe A., Tachiwana H., Horikoshi Y., Fukuto A., Matsuda R., Ura K., Tashiro S., Ikura T., and Kurumizaka H.
  • Organizer: The 4D Nucleome
  • Place of Presentation: 安芸グランドホテル(広島県)
  • Year and Date: 2014-12-17 – 2014-12-20
• [Presentation] Nap1は高次クロマチンでの相同組換えを促進する (2014)
  • Author(s): 町田晋一、高久誉大、井倉正枝、孫継英、鈴木秀和、小林航、木野村愛子、越阪部晃永、立和名博昭、堀越保則、福戸敦彦、松田諒、浦聖恵、田代聡、井倉毅、胡桃坂仁志
  • Organizer: 第32回染色体ワークショップ・第13回核ダイナミクス研究会合
  • Place of Presentation: 安芸グランドホテル(広島県)
  • Year and Date: 2014-12-15 – 2014-12-17
• [Presentation] Biochemical analyses of the RAD51-mediated homologous pairing in chromatin containing the linker histone variant, H1T. (2014)
  • Author(s): Shinichi Machida, Ryota Hayashida, and Hitoshi Kurumizaka
  • Organizer: 3R Symposium
  • Place of Presentation: 御殿場高原ホテル(静岡県)
  • Year and Date: 2014-11-17 – 2014-11-21
• [Presentation] リンカーヒストンバリアントH1Tの相同組換えにおける機能 (2014)
  • Author(s): 町田晋一、林田亮太、加藤大貴、越阪部晃永、小林航、胡桃坂仁志
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2014-10-15 – 2014-10-18