Histone synthesis during the cell cycle of Physarum polycephalum. Synthesis of different histone species is not under a common regulatory control.

The synthesis of histones and nonhistone nuclear proteins was studied during the naturally synchronous cell cycle of Physarum polycephalum. Contrary to the commonly accepted idea of a tight coupling of histone biosynthesis and DNA replication during the somatic cell cycle we found that 40% of total histone synthesis takes place in the G2 period in the complete absence of DNA synthesis. The core histones exhibit a maximum of synthesis during S-phase. The synthesis of histones H2A and H2B continues during the G2 period, but synthesis of H4 and H3 is restricted to the S-phase of the cell cycle. Experiments with hydroxyurea demonstrated that the synthesis of H4 and H3 is completely dependent on unperturbed DNA synthesis, whereas synthesis of H2A and H2B is independent from DNA synthesis during the entire cell cycle. This implicates significant differences between the arginine-rich histones H4 and H3 and the moderately lysine-rich histones H2A and H2B with respect to the control mechanisms of their synthesis, the metabolic stability, and the function for chromatin structure. The nonhistone nuclear proteins are synthesized throughout the cell cycle with a broad maximum in the early G2 period. The cell cycle pattern of synthesis of H1 rather resembles the pattern of the nonhistone proteins than of core histones.