Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1

Cohesion between sister chromatids is established during DNA replication an d depends on a multiprotein complex called cohesin. Attachment of sister ki netochores to the mitotic spindle during mitosis generates forces that woul d immediately split sister chromatids were it not opposed by cohesion. Cohe sion is essential for the alignment of chromosomes in metaphase but must be abolished for sister separation to start during anaphase. In the budding y east Saccharomyces cerevisiae, loss of sister-chromatid cohesion depends on a separating protein (separin) called Esp 1 and is accompanied by dissocia tion from the chromosomes of the cohesion subunit Scc1. Here we show that E sp1 causes the dissooiation of Scc1 from chromosomes by stimulating its cle avage by proteolysis. A mutant Scc1 is described that is resistant to Esp1- dependent cleavage and which blocks both sister-chromatid separation and th e dissociation of Scc1 from chromosomes. The evolutionary conservation of s eparins indicates that the proteolytic cleavage of cohesion proteins might be a general mechanism for triggering anaphase.