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

Gabriela Alexandru, Frank Uhlmann, Karl Mechtler, Marc-André Poupart, Kim Nasmyth

    Research output: Contribution to journalArticlepeer-review

    300 Citations (Scopus)

    Abstract

    At the onset of anaphase, a caspase-related protease (separase) destroys the link between sister chromatids by cleaving the cohesin subunit Scc1. During most of the cell cycle, separase is kept inactive by binding to an inhibitory protein called securin. Separase activation requires proteolysis of securin, which is mediated by an ubiquitin protein ligase called the anaphase-promoting complex. Cells regulate anaphase entry by delaying securin ubiquitination until all chromosomes have attached to the mitotic spindle. Though no longer regulated by this mitotic surveillance mechanism, sister separation remains tightly cell cycle regulated in yeast mutants lacking securin. We show here that the Polo/Cdc5 kinase phosphorylates serine residues adjacent to Scc1 cleavage sites and strongly enhances their cleavage. Phosphorylation of separase recognition sites may be highly conserved and regulates sister chromatid separation independently of securin.

    Original languageEnglish
    Pages (from-to)459-472
    Number of pages14
    JournalCell
    Volume105
    Issue number4
    DOIs
    Publication statusPublished - 2001

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