Cyclin A2 localises in the cytoplasm at the S/G2 transition to activate Plk1

Cyclin A2 is a key regulator of the eukaryotic cell cycle. By forming complexes with Cdk1 and Cdk2, Cyclin A2 regulates both spatial and temporal phosphorylation of target proteins, particularly during S and G2 phases. Here we describe a change in localisation of Cyclin A2 from being only nuclear to both nuclear and cytoplasmic at the S/G2 border. Inflicting DNA damage in G2 phase led to a complete loss of cytoplasmic Cyclin A2 in a manner that depended on p53 and p21. In the absence of externally induced DNA damage, p21-/- cells showed increased cytoplasmic localisation of Cyclin A2. In addition, depletion of Cdk1 delayed accumulation of cytoplasmic Cyclin A2, suggesting that the combined action of Cdk1 and p21 can modulate Cyclin A2 localisation. Interestingly, Cyclin A2 localisation change occurs simultaneously with Plk1 kinase activation, and we provide evidence that cytoplasmic Cyclin A2 can activate Plk1. We propose that cytoplasmic appearance of Cyclin A2 at the S/G2 transition could function as the long sought for trigger for mitotic kinase activation.