Use of a cell cycle mutant to delineate the critical period for the control of histone mRNA levels in the mammalian cell cycle.

Temporal analysis of DNA replication and histone mRNA accumulation in a hamster fibroblast cell cycle mutant (K12) showed that histone mRNA accumulates periodically during the cell cycle and reaches its highest level in the S phase. The direct correlation between the initiation of DNA synthesis and the accumulation of histone mRNA to high levels in S phase demonstrated the strict interdependence of these two events. Moreover, a critical period necessary for histone mRNA accumulation occurred late in G1 phase. If cells were incubated at the nonpermissive temperature during this critical period, the amount of histone mRNA remained at the basal level. Transcription rate measurements indicated that the triggering of histone mRNA synthesis occurred in late G1 and this mRNA was synthesized at its maximal rate 3 to 5 h before its peak of accumulation. However, if cells were prohibited from synthesizing DNA as a consequence of the temperature-sensitive block in G1, the synthesis of histone mRNA was not initiated.