Scc2 counteracts a Wapl-independent mechanism that releases cohesin from chromosomes during G1 but is unnecessary during S phase for establishing cohesion

SummaryCohesin’s association with chromosomes is determined by loading dependent on the Scc2/4 complex and release due to Wapl. We show here that Scc2/4 is not merely a loading complex and that it actively maintains cohesin on chromosomes during G1. It does so by blocking a Wapl-independent release reaction that requires opening the cohesin ring at its Smc3/Scc1 interface as well as the D loop of Smc1’s ATPase. The Wapl-independent release mechanism is switched off as cells activate Cdk1 and enter G2/M and cannot be turned back on without cohesin’s dissociation from chromosomes. The latter phenomenon enabled us to show that cohesin that has already captured DNA in a Scc2-dependent manner before replication no longer requires Scc2 to capture sister DNAs during S phase.