Deciphering the modes of human separase inhibition by securin and CDK1-CCNB1

Abstract

Accurate chromosome segregation depends on tight regulation of the protease separase, which cleaves the ring-shaped cohesin complex that entraps the two sister chromatids. We recently reported structures of human separase bound to its inhibitors securin or the cyclin-dependent kinase 1 (CDK1)-cyclin B1 (CCNB1)-cyclin-dependent kinases regulatory subunit 1 (CKS1) complex and discovered an array of molecular mechanisms that block cohesin-cleavage.

Keywords

• cell cycle
• cohesin
• autoinhibition
• substrate occlusion
• caspase
• oncogene
• mitosis