Micromechanics of the mitotic chromosome

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19362
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Molecular and Genome biology and related fields
• 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): 2017-06-30 – 2020-03-31
• Keywords: 染色体 / 紡錘体 / 動原体 / 細胞分裂 / 力計測

Outline of Final Research Achievements

We studied the mechanical properties of the human mitotic chromosome, in the light of elucidating the physical and molecular basis ensuring the genomic fidelity in cell division. Instabilities in chromosome number or structure are linked to life-threatening diseases such as cancer. We know that these instabilities are related to physical force that acts on chromosomes in cell division, but how force indeed impacts the chromosome dynamics remains poorly understood. We address this issue by developing a microneedle-based quantitative micromanipulation setup that allowed us to apply controlled force to specific loci on chromosomes. Our data suggest that the region around the kinetochore, which is the structural hub connecting the spindle appartus with the chromosome, is soft and elastic, being easiliy deformable against a pulling force but restoring its original shape upon removal of the force. We also observed a robust deformation mechanics at a site distant to the kinetochore.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

遺伝情報のキャリアである染色体に生じる機械的欠陥は、がんなどの重要な疾患と関連する。本研究で開発した分裂期ヒト染色体の顕微力学計測・操作システムは、染色体が持つ機械的性質を単一オルガネラレベルで直接、定量的に解析評価することを可能にしたものである。染色体が分裂期の細胞内で機械的なシグナルや摂動を受けながらそのインテグリティを維持するための物理的・分子的基盤が明らかになることで、遺伝的フィデリティの維持メカニズムについての根本的な理解が可能となり、得られた知見は新たな疾患治療戦略創出の一助となることが期待される。