Cohesin loop extrusion tethers DNA replication forks to drive their slowing and reversal II

How genome architectural factors influence this response is poorly understood. Here, we investigated the role of cohesin and its different functions by the use of auxin-inducible degrons (AID) and separation of function mutants.

With a newly-developed Micro-C based technique to capture chromatin contacts at nascent DNA (Repli-C), we describe that loop-extruding cohesin helps tethering replication forks in proximal chromosomal regions, including those departed from adjacent replication origins. Replication stress strengthens these contacts by promoting cohesin stabilization at forks. This process promotes replication fork reversal and active fork slowing, by preventing PRIMPOL action on ssDNA.