The little condensins that could: How tiny condensins move colossal chromosomes

During cell division hundreds of thousands of 5nm long condensin molecules come together to fold the micrometer long chromosomes by loop extrusion. However, experimental data is available either at the 5nm scale (as single molecule experiments) or at the micron scale (as Hi-C). Thus, we built a kinetic model of multiple condensins that can bridge this gap in length scales. The loops from the kinetic model are used as a scaffold in a generalized rouse model to create chromosome structures. We call this an Active Generalized Rouse Model for chromosomes (A-GRMC). The A-GRMC model can accurately reproduce the experimentally measured contact probability profiles in HeLa and DT40 cells without any parameter fit. We show that complex loop architectures such as Z-loops or nested loops arise in the mitotic chromosomes. These loops are stapled to a dynamically changing backbone formed by the motors. The model also lets us predict that loop extrusion speeds up as mitosis progresses. This work is the first theoretical study of mitotic chromosomes with active loop extrusion.