DNA passes through cohesin's hinge as well as its Smc3-kleisin interface

The ring model proposes that sister chromatid cohesion is mediated by co-entrapment of sister DNAs inside a single tripartite cohesin ring. The model explains how Scc1 cleavage triggers anaphase but has hitherto only been rigorously tested using small circular mini-chromosomes in yeast, where covalently circularizing the ring by crosslinking its three interfaces induces catenation of individual and sister DNAs. If the model applies to real chromatids, then the ring must have a DNA entry gate essential for mitosis. Whether this is situated at the Smc3/Scc1 or Smc1/Smc3 hinge interface is an open question. We have previously demonstrated DNA entrapment by cohesin in vitro (Collier et al., 2020). Here we show that cohesin in fact possesses two DNA gates, one at the Smc3/Scc1 interface and a second at the Smc1/3 hinge. Unlike the Smc3/Scc1 interface, passage of DNAs through SMC hinges depends on both Scc2 and Scc3, a pair of regulatory subunits necessary for entrapment in vivo. This property together with the lethality caused by locking this interface but not that between Smc3 and Scc1 in vivo suggests that passage of DNAs through the hinge is essential for building sister chromatid cohesion. Passage of DNAs through the Smc3/Scc1 interface is necessary for cohesin's separase-independent release from chromosomes and may therefore largely serve as an exit gate.

Automated summary

The ring model proposes that sister chromatid cohesion is mediated by the entrapment of sister DNAs inside a cohesin ring. Previous studies have only tested this model using small circular mini-chromosomes in yeast. In this study, the researchers demonstrate that cohesin possesses two DNA gates, one at the Smc3/Scc1 interface and a second at the Smc1/3 hinge. Passage of DNAs through the hinge is essential for building sister chromatid cohesion, while passage through the Smc3/Scc1 interface is necessary for cohesin's release from chromosomes.