The Molecular Logic of the Centrosome Duplication Cycle

The centrosome organizes the microtubule cytoskeleton and consists of a pair of centrioles surrounded by pericentriolar material. Cells begin the cell cycle with a single centrosome, which duplicates once prior to mitosis. During duplication, new centrioles grow orthogonally to existing centrioles and remain engaged with those centrioles until late mitosis, when they become disengaged. We have found that centriole disengagement requires the separase protease at anaphase, and that disengagement licenses centrioles for duplication in the next cell cycle. Using an in vitro system we show that centriole disengagement at anaphase is independent of mitotic exit and Cdk2/E activity, but requires the anaphase promoting complex (APC) and separase. In contrast to disengagement, new centriole growth occurs in interphase, requires Cdk2/E, and requires previously disengaged centrioles. This suggests that reduplication of centrioles within a cell cycle is prevented by centriole engagement itself. We propose that the once‐and‐only‐once control of centrosome duplication is achieved by temporally separating licensing in anaphase from growth of new centrioles during S phase. The involvement of separase in both centriole disengagement and sister chromatid separation would prevent premature centriole disengagement before anaphase onset, which can lead to multipolar spindles and genome instability.