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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We thank Dr J Lazo for the compound 5 cdc25 inhibitor and Dr David Morgan for the cdk2 wt and AF constructs. This study was supported by grants from the Queensland Cancer Fund and the National Health and Medical Research Council of Australia. S Goldstone was supported as a CJ Martin Fellow of the National Health and Medical Research Council of Australia. B Gabrielli is an Australian Research Council Fellow.
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Goldstone, S., Pavey, S., Forrest, A. et al. Cdc25-dependent activation of cyclin A/cdk2 is blocked in G2 phase arrested cells independently of ATM/ATR. Oncogene 20, 921–932 (2001). https://doi.org/10.1038/sj.onc.1204177
- cell cycle checkpoint
- DNA damage
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