A unified model for cohesin function in sister chromatid cohesion and chromatin loop formation

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Abstract

The ring-shaped cohesin complex topologically entraps two DNAs to establish sister chromatid cohesion. Cohesin also shapes the interphase chromatin landscape by forming DNA loops, which it is thought to achieve using an in vitro-observed loop extrusion mechanism. However, recent studies revealed that loop-extrusion-deficient cohesin retains its ability to form chromatin loops, suggesting a divergence of in vitro and in vivo loop formation. Instead of loop extrusion, we examine whether cohesin forms chromatin loops by a mechanism akin to sister chromatid cohesion establishment: sequential topological capture of two DNAs. We explore similarities and differences between the "loop capture" and the "loop extrusion" model, how they compare at explaining experimental observations, and how future approaches can delineate their possible respective contributions. We extend our DNA-DNA capture model for cohesin function to related structural maintenance of chromosomes (SMC) family members, condensin, the Smc5-Smc6 complex, and bacterial SMC complexes.