Co-ordinate control of centrosomal separation and DNA synthesis by growth regulators

We have tested the effects of various mitogens and growth inhibitors on centrosomal separation (CS) in serum-deprived HeLa, gerbil fibroma (GF) and A431 cells. All of the agents which were mitogenic in a given cell type also stimulated CS. No agent was found which stimulated CS but failed to stimulate DNA synthesis. Inhibitors of DNA synthesis, including somatostatin, hydrocortisone, 8-bromo-cAMP, and epidermal growth factor (EGF) in A431 cells, also inhibited CS in response to mitogens. In GF cells (blocked at the G1/S interface with hydroxyurea) centrosomal re-association and the decay in commitment to DNA synthesis upon serum withdrawal occurred with a similar t1/2 (8.8 h). These results demonstrate that CS and DNA synthesis are co-ordinately regulated by a variety of stimulators and inhibitors of cell proliferation. Separation of the centrosomes, or an underlying event with which it is tightly coupled, may represent the point of cellular commitment to enter S phase.