Our objective is to elucidate the mechanisms regulating histone biosynthesis in G1, S and GO. Using methodology developed in our group over the last several years to resolve and characterize histone variants, we have been analyzing the patterns of histone synthesis during different cell behavioral states. Histones were found to be synthesized not only during S-phase, but also during G1 and the quiescent state (also termed extended G1 or G0). The qualitative pattern of histone synthesis differs between S-phase, G1 and quiescent cells, a finding which shows that the synthesis in G1 or quiescent cells is not due to contamination by S-phase cells. The histone synthesis in both G1 and quiescent cells is not linked to DNA synthesis. Histones synthesized in quiescent cells are stable and seem to be incorporated into chromatin. The results suggest that the quiescent state is not an extended G1 phase but a discrete state. This year, we published a comprehensive model concerning the regulation of histone and DNA synthesis. The cytoplasmic histone pool is a crucial factor in this model and methods for analyzing the histone pool are being worked out. There is some evidence in the literature which suggests that there may be significant differences in the regulation of chromatin biosynthesis between normal and tumorigenic cells. Understanding these differences may lead to the development of protocols to protect normal cells or make tumorgenic cells more vulnerable to various treatments.
