Mechanosensing properties of mitotic chromosomes and chromosome assembly factors

• Project/Area Number: 19H03201
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43040:Biophysics-related
• Research Institution: National Institute of Genetics
• Principal Investigator: Shimamoto Yuta 国立遺伝学研究所, 遺伝メカニズム研究系, 准教授 (80409656)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2019: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 染色体 / 紡錘体 / 細胞分裂 / 力学特性 / 有志分裂 / 微小管 / 力計測 / 染色体分配 / 力学測定 / 有糸分裂 / 力学計測 / 力 / オルガネラ / 一分子計測

Outline of Research at the Start

遺伝情報の保持と継承を担う染色体が細胞分裂期に受ける力のシグナルやストレスに適切に応答・対抗するしくみを調べるため、生物物理の力計測ツールを基礎とした顕微解析装置を開発する。これを用いて染色体の力学応答特性を分子、オルガネラ、細胞レベルの各階層で定量的に決定し、親細胞から娘細胞への遺伝情報継承がこのオルガネラの物性によっていかに保証され、またそれがいかに破綻するかを明らかにする。

Outline of Final Research Achievements

This research project aimed at elucidating the biophysical properties of mitotic chromosomes in vertebrates. A novel assay integrating Xenopus egg cytoplasmic extracts with high-resolution confocal fluorescence imaging and force-calibrated microneedles allowed us to determine the force sensitivity of sister chromatid cohesion in anaphase and the contribution of topoisomerase II, a DNA decatenation enzyme. The project also involved the development and use of in vitro assays dissecting the mechanical properties of single mitotic chromosomes and DNA-crosslinking molecules such as cohesin and topoisomerase II.

Academic Significance and Societal Importance of the Research Achievements

遺伝情報を格納する染色体の力学応答特性を高分解能で測ることのできる顕微鏡システムを開発し、細胞分裂期に染色体が示す機械感受性と背後の分子メカニズムを明らかにした。この機械感受性の消失は染色体の異数化やDNA損傷の原因となる可能性があり、がんなどの関連疾病のメカニズム解明に貢献する重要な生物物理学的知見となることが期待される。

Research Products

• [Int'l Joint Research] University of Wisconsin-Madison(米国)
• [Journal Article] Local body weight measurement of the spindle (2021)
  • Author(s): Tanaka Masahito、Shimamoto Yuta
  • Journal Title: Developmental Cell Volume: 56 Issue: 7 Pages: 871-872
  • DOI: 10.1016/j.devcel.2021.03.019
  • Peer Reviewed / Open Access
• [Journal Article] Mechanics of Cell Division (2020)
  • Author(s): Shimamoto Yuta、Redemann Stefanie、Needleman Daniel
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 8
  • DOI: 10.3389/fcell.2020.620111
  • Open Access / Int'l Joint Research
• [Journal Article] Examining the assembly pathways and active microtubule mechanics underlying spindle selforganization (2020)
  • Author(s): Lucan Yan, Tatsuya Fukuyama, Megumi Yamaoka, Yusuke T. Maeda, Yuta Shimamoto
  • Journal Title: arXiv Volume: -
  • Open Access
• [Presentation] オルガネラ・細胞内構造体のマイクロメカニクス (2022)
  • Author(s): 島本勇太
  • Organizer: 第7回Organelle Zoneセミナー
  • Invited
• [Presentation] 機械計測と摂動操作でオルガネラ・細胞内構造体の力学特性を明らかにする (2021)
  • Author(s): 島本勇太
  • Organizer: 第44回日本分子生物学会年会
  • Invited
• [Presentation] Measuring and perturbing the micromechanics of intracellular structures (2021)
  • Author(s): 島本勇太
  • Organizer: 第60回日本生体医工学会大会
  • Invited
• [Presentation] Mesoscale microtubule mechanics controlling the assembly and function of the chromosome segregation machinery (2020)
  • Author(s): Yuta Shimamoto
  • Organizer: 第58回日本生物物理学会年会
  • Invited
• [Presentation] Biophysical approaches to elucidate the principle of spindle assembly in cell division (2020)
  • Author(s): Yuta Shimamoto
  • Organizer: 第43回日本分子生物学会年会
  • Invited
• [Presentation] Micromechanics of cell division: Deciphering the forces that underlie spindle assembly and chromosome segregation (2019)
  • Author(s): Yuta Shimamoto
  • Organizer: NIG Biological Symposium
• [Presentation] Examining the emergent mechanics underlying the vertebrate spindle assembly and force generation (2019)
  • Author(s): Yuta Shimamoto
  • Organizer: 第９回分子モーター討論会
• [Presentation] Examining the meiotic spindle micromechanics using cell-free extracts and quantitative micromanipulation (2019)
  • Author(s): Yuta Shimamoto
  • Organizer: 第92回日本生化学会大会
  • Int'l Joint Research
• [Presentation] Probing the local mechanical architecture of the vertebrate metaphase spindle (2019)
  • Author(s): Yuta Shimamoto
  • Organizer: ASCB/EMBO annual meeting
  • Int'l Joint Research
• [Presentation] 紡錘体の構築原理と力学デザイン (2019)
  • Author(s): 島本勇太
  • Organizer: 第37 回 染色体ワークショップ 第18 回 核ダイナミクス研究会