Cohesin Cleavage by Separase Required for Anaphase and Cytokinesis in Human Cells

TLDR

Cell division requires sister chromatid separation, which in yeast is driven by separase‑mediated cohesin cleavage, whereas vertebrates largely remove cohesin from chromosome arms by a cleavage‑independent mechanism, with only a small amount of centromeric cohesin cleaved at anaphase onset. We identified two separase cleavage sites in human SCC1 and expressed non‑cleavable SCC1 mutants to assess their role. Cohesin cleavage by separase is essential for sister chromatid separation and for completing cytokinesis.

Abstract

Cell division depends on the separation of sister chromatids in anaphase. In yeast, sister separation is initiated by cleavage of cohesin by the protease separase. In vertebrates, most cohesin is removed from chromosome arms by a cleavage-independent mechanism. Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres. We have identified two separase cleavage sites in the human cohesin subunit SCC1 and have conditionally expressed noncleavable SCC1 mutants in human cells. Our results indicate that cohesin cleavage by separase is essential for sister chromatid separation and for the completion of cytokinesis.