Muschel R J, Zhang H B, Iliakis G, McKenna W G
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104.
Cancer Res. 1991 Oct 1;51(19):5113-7.
After exposure to ionizing radiation, eukaryotic cells undergo a division delay which is reflected by increased time spent in the G2 portion of the cell cycle. Recent information identifies increased levels of mitotic cyclins as key biochemical events initiating mitosis. In HeLa cells cyclin B mRNA and protein levels have been shown to increase in G2 and to decrease after division is completed. Cyclin B protein binds to cdc2, resulting in histone kinase activity which is necessary for the initiation of mitosis. Accordingly, we chose to investigate how cyclin B mRNA and protein levels were perturbed by irradiation in order to gain further understanding of the mechanisms by which ionizing radiation leads to a division delay. Our experiments revealed at least two effects on cyclin B regulation which might contribute to the division delay: (a) when HeLa cells were irradiated in S phase, there was a delay in the accumulation of cyclin B mRNA; (b) when cells were radiated in G2 phase, at a time when mRNA levels were increasing, a division delay was induced which coincided with a markedly lowered level of cyclin B protein despite high levels of the mRNA.
