Secured cutting: controlling separase at the metaphase to anaphase transition

The final irreversible step in the duplication and distribution of genomes to daughter cells takes place at the metaphase to anaphase transition. At t his point aligned sister chromatid pairs split and separate. During metapha se, cohesion between sister chromatids is maintained by the chromosomal mul ti-subunit cohesin complex. Here, I review recent findings as to how anapha se is initiated by proteolytic cleavage of the Scc1 subunit of cohesin. Scc 1 is cleaved by a site-specific protease that is conserved in all eukaryote s, and is now called 'separase'. As a result of this cleavage, the cohesin complex is destroyed, allowing the spindle to pull sister chromatids into o pposite halves of the cell. Because of the final and irreversible nature of Scc1 cleavage, this reaction is tightly controlled. Several independent me chanisms seem to impose regulation on Scc1 cleavage, acting on both the act ivity of separase and the susceptibility of the substrate.