Cohesin-mediated DNA loop extrusion resolves sister chromatids in G2 phase

Genetic information is stored in linear DNA molecules, which are highly folded inside cells. DNA replication along the folded template path yields two sister chromatids that initially occupy the same nuclear region in an intertwined arrangement. Dividing cells must disentangle and condense the sister chromatids into separate bodies such that a microtubule-based spindle can move them to opposite poles. While the spindle-mediated transport of sister chromatids has been studied in detail, the chromosome-intrinsic mechanics presegregating sister chromatids have remained elusive. Here, we show that human sister chromatids resolve extensively already during interphase, in a process dependent on the loop-extruding activity of cohesin, but not that of condensins. Increasing cohesin's looping capability increases sister DNA resolution in interphase nuclei to an extent normally seen only during mitosis, despite the presence of abundant arm cohesion. That cohesin can resolve sister chromatids so extensively in the absence of mitosis-specific activities indicates that DNA loop extrusion is a generic mechanism for segregating replicated genomes, shared across different Structural Maintenance of Chromosomes (SMC) protein complexes in all kingdoms of life.

Automated summary

Genetic information is stored in folded linear DNA molecules inside cells. During cell division, sister chromatids need to be disentangled and condensed into separate bodies for proper separation. In human cells, sister chromatids are extensively resolved during interphase, depending on the loop-extruding activity of cohesin. Increasing cohesin's looping capability can further enhance sister DNA resolution, even in the absence of mitosis-specific activities.