Releasing Activity Disengages Cohesin’s Smc3/Scc1udInterface in a Process Blocked by Acetylation

摘要

Sister chromatid cohesion conferred by entrapmentudof sister DNAs within a tripartite ring formed betweenudcohesin’s Scc1, Smc1, and Smc3 subunits is createdudduring S and destroyed at anaphase through Scc1udcleavage by separase. Cohesin’s association withudchromosomes is controlled by opposing activities:udloading by Scc2/4 complex and release by a separase-udindependent releasing activity as well as byudcleavage. Coentrapment of sister DNAs at replicationudis accompanied by acetylation of Smc3 by Eco1,udwhich blocks releasing activity and ensures that sistersudremain connected. Because fusion of Smc3 toudScc1 prevents release and bypasses the requirementudfor Eco1, we suggested that release is mediatedudby disengagement of the Smc3/Scc1 interface. Weudshow that mutations capable of bypassing Eco1 inudSmc1, Smc3, Scc1, Wapl, Pds5, and Scc3 subunitsudreduce dissociation of N-terminal cleavage fragmentsudof Scc1 (NScc1) from Smc3. This process involvesudinteraction between Smc ATPase heads andudis inhibited by Smc3 acetylation.