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EMBO reports 2, 6, 487–492 (2001)
doi:10.1093/embo-reports/kve113
Secured cutting: controlling separase at the metaphase to anaphase transition
Frank Uhlmann
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Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
To whom correspondence should be addressed
Frank Uhlmann Tel: +44 207 269 3024; Fax: +44 207 269 3581; f.uhlmann@icrf.icnet.uk
Received 27 October 2000; Accepted 24 April 2001.
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Abstract
The final irreversible step in the duplication and distribution of genomes to daughter cells takes place at the metaphase to anaphase transition. At this point aligned sister chromatid pairs split and separate. During metaphase, cohesion between sister chromatids is maintained by the chromosomal multi-subunit cohesin complex. Here, I review recent findings as to how anaphase is initiated by proteolytic cleavage of the Scc1 subunit of cohesin. Scc1 is cleaved by a site-specific protease that is conserved in all eukaryotes, and is now called 'separase'. As a result of this cleavage, the cohesin complex is destroyed, allowing the spindle to pull sister chromatids into opposite halves of the cell. Because of the final and irreversible nature of Scc1 cleavage, this reaction is tightly controlled. Several independent mechanisms seem to impose regulation on Scc1 cleavage, acting on both the activity of separase and the susceptibility of the substrate.
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