Elucidation of condensin-mediated control of DNA supercoiling and and its physiological roles

• Project/Area Number: 17K07281
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: The University of Tokyo
• Principal Investigator: Sutani Takashi 東京大学, 定量生命科学研究所, 講師 (30401524)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 染色体 / 染色体凝縮 / コンデンシン / Smc5/6 / DNA超らせん / 染色体高次構造 / DNAトポロジー / Hi-C / ゲノム / バイオインフォマティクス

Outline of Final Research Achievements

In this study, we aimed to elucidate how condensin, a key player of mitotic chromosome condensation, drives chromosome condensation at molecular level. Research did not progress as initially planned due to technical difficulties. However, we obtained the results showing that the condensin-like Smc5/6 complex recognized chromosomal regions with accumulated DNA positive supercoiling. This result is important for understanding the molecular function of Smc5/6. It also implies that Smc5/6 can be used as a probe protein to measure the supercoiling state of DNA.

Academic Significance and Societal Importance of the Research Achievements

コンデンシンやSmc5/6複合体は、遺伝情報が子孫細胞に正確に伝達されてゆくために不可欠な役割を果たす因子である。これらの因子の機能異常は発がんや先天性遺伝疾患の原因となることが知られている。本研究成果はコンデンシンやSmc5/6複合体が細胞内で果たす役割を明らかにする一歩となるものである。染色体凝縮などの染色体高次構造の制御においてDNA超らせんが果たす役割は、これまでにも示唆はされているが、未解明の部分が大きい。これは染色体DNAの超らせん状態を計測する手法が整備されていないためである。本研究の知見を活用すると、超らせん状態計測の新技法が開発できる可能性がある。

Research Products

• [Int'l Joint Research] Karolinska Institutet(スウェーデン)
• [Int'l Joint Research] Karolinska Institutet(スウェーデン)
• [Journal Article] ChIP-seq analysis of condensin complex in cultured mammalian cells (2017)
  • Author(s): Sakata, T., Shirahige, K., Sutani, T.
  • Journal Title: Methods in Molecular Biology Volume: 1515 Pages: 257-271
  • DOI: 10.1007/978-1-4939-6545-8_16
  • ISBN: 9781493965434, 9781493965458
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Behavior of cohesive cohesin complex on human chromosomes (2019)
  • Author(s): Takashi Sutani, Mai Ishibashi, Masashige Bando, Atsunori Yoshimura, Katsuhiko Shirahige
  • Organizer: EMBO workshop “Organization of bacterial and eukaryotic genomes by SMC complexes”
  • Int'l Joint Research
• [Presentation] Characteristics of Smc5/6 binding sites revealed by machine learning-based modeling (2018)
  • Author(s): Takashi Sutani, Kristian Jeppsson, Katsuhiko Shirahige, Camilla Bjorkengren
  • Organizer: The 11th 3R & 3C symposium
  • Int'l Joint Research
• [Presentation] Physical association of S. cerevisiae polo-like kinase Cdc5 with chromosomal cohesin facilitates DNA damage response (2017)
  • Author(s): Sujiraporn Pakchuen、Mai Ishibashi、Katsuhiko Shirahige、Takashi Sutani
  • Organizer: 2nd meeting on SMC proteins
  • Int'l Joint Research