Our objective is to understand the relationship of various cell states and the transitions between them as reflected in the control of histone and chromatin biosynthesis. One phenomenon which we have studied is the differential sensitivity of the growth and chromosome cycles to the rate of protein synthesis. The chromosome cycle seems to be relatively invariant even though other results show that DNA synthesis is inhibited in parallel to the inhibition of protein synthesis. To resolve this apparent paradox, we studied histone and DNA synthesis under different conditions of protein synthesis and cell growth. We have found and characterized a phenomenon which we have named chromosome cycle compensation. As protein synthesis is inhibited, the mRNA level of S-phase histones rises to compensate for the inefficiency of protein synthesis. There is evidence in the literature that normal and tumorigenic cells may differ significantly in their level of chromosome cycle compensation. Understanding this mechanism may lead to some insights into the growth characteristics of normal and tumorigenic cells.
