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Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events

Abstract

Cyclin A/cdk2 has a role in progression through S phase, and a large pool is also activated in G2 phase. Here we report that this G2 phase pool regulates the timing of progression into mitosis. Knock down of cyclin A by siRNA or addition of a specific cdk2 small molecule inhibitor delayed entry into mitosis by delaying cells in G2 phase. The G2 phase-delayed cells contained elevated levels of inactive cyclin B/cdk1. However, increased microtubule nucleation at the centrosomes was observed, and the centrosomes stained for markers of cyclin B/cdk1 activity. Both microtubule nucleation at the centrosomes and the phosphoprotein markers were lost with short-term treatment of the cdk1/2 inhibitor roscovitine but not the Mek1/2 inhibitor U0126. Cyclin A/cdk2 localized at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Thus G2 phase cyclin A/cdk2 controls the timing of entry into mitosis by controlling the subsequent activation of cyclin B/cdk1, but also has an unexpected role in coordinating the activation of cyclin B/cdk1 at the centrosome and in the nucleus.

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Acknowledgements

We thank both the National Health and Medical Research Council of Australia and Queensland Cancer Fund for funding, Dr Nicole den Elzen and Dr Rose Boutros for advice and critical reading of the paper and all other members of the Gabrielli laboratory for critical advice. HB is supported with a Lions Medical Research Fellowship and BG is supported with an NHMRC Senior Research Fellowship.

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Correspondence to B Gabrielli.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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De Boer, L., Oakes, V., Beamish, H. et al. Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events. Oncogene 27, 4261–4268 (2008). https://doi.org/10.1038/onc.2008.74

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