Functional analysis of separase and its novel substrate in the licensing of centrosome duplication

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Centrosome assembles the bipolar spindle during mitosis to ensure the equal segregation of replicated chromosomes. It is thereby assumed that the licensing mechanism tightly regulates the initiation of centrosome duplication only once per cell cycle, though precise process remains largely unknown. Separase, a cysteine protease that triggers sister chromatid separation, is known to be involved in this licensing, however, its centrosomal substrate remains unidentified. In this study, we found that the centrosomal protein kendrin is cleaved by separase at a consensus site. Moreover, expression of a non-cleavable kendrin mutant suppresses the initiation of centrosome duplication. Our finding provides the first evidence that kendrin is a novel and crucial substrate for separase at the centrosome involved in the licensing of centrosome duplication.