Bridging condensins mediate compaction of mitotic chromosomes

G Forte and L Boteva and F Conforto and N Gilbert and PR Cook and D Marenduzzo, JOURNAL OF CELL BIOLOGY, 223, e202209113 (2023).

DOI: 10.1083/jcb.202209113

Forte et al. report simulations revealing that bridging condensins are important to condense chromosomes into mitotic cylinders. This work underscores the importance of the bridging, as well as looping, activity of condensins, and points to a mechanistic model for chromatin structure at chromosome fragile sites. Eukaryotic chromosomes compact during mitosis into elongated cylinders-and not the spherical globules expected of self-attracting long flexible polymers. This process is mainly driven by condensin-like proteins. Here, we present Brownian-dynamic simulations involving two types of such proteins with different activities. One, which we refer to as looping condensins, anchors long- lived chromatin loops to create bottlebrush structures. The second, referred to as bridging condensins, forms multivalent bridges between distant parts of these loops. We show that binding of bridging condensins leads to the formation of shorter and stiffer mitotic-like cylinders without requiring any additional energy input. These cylinders have several features matching experimental observations. For instance, the axial condensin backbone breaks up into clusters as found by microscopy, and cylinder elasticity qualitatively matches that seen in chromosome pulling experiments. Additionally, simulating global condensin depletion or local faulty condensin loading gives phenotypes seen experimentally and points to a mechanistic basis for the structure of common fragile sites in mitotic chromosomes.

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