Differential effect of ionizing radiation on the expression of cyclin A and cyclin B in HeLa cells.

Ionizing radiation induces a G2 delay in eukaryotic cells. Since mitotic cyclins are required to trigger the transition from G2 into and through mitosis, we chose to investigate their expression after irradiation in HeLa cells. In normally cycling HeLa cells, both cyclin A and B mRNA and protein levels rise dramatically in G2/M and rapidly fall coincident with the completion of mitosis. The rise of cyclin A mRNA at the S/G2 boundary slightly precedes that of cyclin B mRNA. Although the peaks of expression of each of these molecules overlap, cyclin A mRNA and protein diminish before cyclin B. After irradiation in S, cyclin A mRNA and protein levels rose with the same kinetics as in the controls, but ultimately exceeded the levels seen in the control population. Cyclin A mRNA and protein levels remained high throughout the G2 delay induced by irradiation. In contrast, cyclin B mRNA and protein levels did not rise as the irradiated cells entered G2/M. Only later, before the irradiated cells exited from G2/M, did levels of cyclin B reach the levels seen in the unirradiated controls. The decreased amount of cyclin B mRNA and protein was inversely proportional to the dose of radiation. These data indicate that irradiation that results in a G2 delay appears to block cells at a point after production of cyclin A but before cyclin B can be fully expressed and that cells do not exit from the delay until cyclin B is again expressed. Thus, cyclin A and cyclin B expression respond differentially to radiation, with cyclin A rising at the same time as the control and to even higher levels than that seen in the controls, whereas cyclin B shows a temporal delay in expression.