The Francis Crick Institute
Browse

Progressive chromosome shape changes during cell divisions.

Download (17.83 MB)
journal contribution
posted on 2025-11-07, 11:42 authored by Yasutaka Kakui, Yoshiharu Kusano, Tereza Clarence, Maya Lopez, Todd Fallesen, Toru Hirota, Bhavin S Khatri, Frank Uhlmann
Mitotic chromosomes give genome portions the required compaction and mechanical stability for faithful inheritance during cell divisions. They are shaped by the chromosomal condensin complex. Here, we record human chromosome dimensions from their appearance in prophase over successive times in a mitotic arrest. Chromosomes first appear long and uniformly thin. Then, individual chromosome arms become discernible, which continuously shorten and thicken-the longer a chromosome arm, the thicker it becomes. In the search for a molecular explanation of this behavior, given uniform condensin density, the popular loop extrusion model provides no obvious means by which longer chromosome arms become thicker. Instead, we find that simulations of an alternative loop capture model recapitulate key features of our observations, with re-arranging chromatin rosettes underpinning the gradually developing arm length-to-width relationship. Our analyses portray chromosomes as out-of-equilibrium structures in the process of transitioning towards, but on biologically relevant time scales not typically reaching, steady state.

Funding

Japan Society for the Promotion of Science London (JSPS) (Grant ID: 22K06092) Japan Society for the Promotion of Science London (JSPS) (Grant ID: 22H04996 and 24H02283) Wellcome Trust (WT) (Grant ID: 220244/Z/20/Z) Wellcome Trust (Grant ID: cc2137) Wellcome Trust (Grant ID: cc2137) Wellcome Trust (Grant ID: cc2137) Waseda University grants for Special Research Projects (Grant ID: 2021C-387,2022C-306,2023C-283,2024C-285) Crick (Grant ID: CC2137, Grant title: Uhlmann CC2137) Crick (Grant ID: CC1069, Grant title: STP Light Microscopy) Wellcome Trust (Grant ID: 220244/Z/20/Z, Grant title: WT 220244/Z/20/Z) Crick (Grant ID: CC2125, Grant title: Molodtsov CC2125)

History