Cdc25-dependent activation of cyclin A/cdk2 is blocked in G2 phase arrested cells independently of ATM/ATR

Oncogene
S GoldstoneBrian Gabrielli

Abstract

Cyclin A/cdk2 is active during S and G2 phases of the cell cycle, but its regulation and function during G2 phase is poorly understood. In this study we have examined the regulation of cyclin A/cdk2 activity during normal G2 phase progression and in genotoxin-induced G2 arrest. We show that cyclin A/cdk2 is activated in early G2 phase by a cdc25 activity. In the G2 phase checkpoint arrest initiated in response to various forms of DNA damage, the cdc25-dependent activation of both cyclin A/cdk2 and cyclin B1/cdc2 is blocked. Ectopic expression of cdc25B, but not cdc25C, in G2 phase arrested cells efficiently activated both cyclin A/cdk2 and cyclin B1/cdc2. Finally, we demonstrate that the block in cyclin A/cdk2 activation in the G2 checkpoint arrest is independent of ATM/ATR. We speculate that the ATM/ATR-independent block in G2 phase cyclin A/cdk2 activation may act as a further layer of checkpoint control, and that blocking G2 phase cyclin A/cdk2 activation contributes to the G2 phase checkpoint arrest.

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Citations

Jan 16, 2002·Current Opinion in Genetics & Development·Dmitry V BulavinAlbert J Fornace
Apr 1, 2008·Oncogene·L De BoerB Gabrielli
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Petronila PenelaFederico Mayor
Oct 6, 2009·The Journal of Biological Chemistry·Puji AstutiBrian Gabrielli
Aug 26, 2009·The Journal of Biological Chemistry·Heather BeamishBrian Gabrielli
Aug 31, 2010·The Journal of Biological Chemistry·Puji AstutiBrian Gabrielli
Jun 10, 2011·F1000 Biology Reports·René H Medema, Libor Macurek
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