To maintain genome stability, centrosome duplication has to be tightly coupled to the cell cycle, as loss of this coupling can lead to centrosome amplification – a common hallmark of cancer cells. Centrosome duplication and DNA replication are controlled by cyclin-dependent kinase 2 (Cdk2), which ensures these processes are only initiated upon S phase entry, i.e. when Cdk2 is active. Centrosome duplication is also regulated in mitosis; here, the disengagement of centrioles that occurs after anaphase onset and licenses them for the next round of replication is controlled by the cysteine protease separase and the mitotic kinase Plk1. On page 5353, Andrew Fry, Suzanna Prosser and colleagues set out to explore the underlying mechanisms behind this control, by arresting cells in G2. They find that G2 arrest promotes premature centriole disengagement, which, as they show, is dependent on Plk1 and separase. Activation of separase is caused by the untimely activation of the anaphase promoting complex (APC/C) in these cells that results from Plk1-mediated loss of the APC/C inhibitor Emi1. Their data also suggest that Plk1 has a second, more direct role in promoting centriole disengagement independent of APC/C. Taken together, these findings suggest that oscillation of APC/C activity in response to cell cycle arrest promotes centrosome amplification and can impact on genome stability.
- © 2012. Published by The Company of Biologists Ltd