Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast

At the onset of anaphase, a caspase-related protease (separase) destroys th e link between sister chromatids by cleaving the cohesin subunit Scc1. Duri ng most of the cell cycle, separase is kept inactive by binding to an inhib itory protein called securin. Separase activation requires proteolysis of s ecurin, which is mediated by an ubiquitin protein ligase called the anaphas e-promoting complex. Cells regulate anaphase entry by delaying securin ubiq uitination until all chromosomes have attached to the mitotic spindle. Thou gh no longer regulated by this mitotic surveillance mechanism, sister separ ation remains tightly cell cycle regulated in yeast mutants lacking securin . We show here that the Polo/Cdc5 kinase phosphorylates serine residues adj acent to Scc1 cleavage sites and strongly enhances their cleavage. Phosphor ylation of separase recognition sites may be highly conserved and regulates sister chromatid separation independently of securin.