Growth-rate-dependent regulation of the expression and inactivation of thymidylate synthase in Saccharomyces cerevisiae.

Thymidylate synthase activity fluctuated dramatically as cultures of Saccharomyces cerevisiae progressed through the different stages of batch culture growth. During logarithmic growth these yeast cultures each contained about 40 microU (1 microU is 1 pmol of 3H released per min) of thymidylate synthase activity per 10(8) haploid cells, but as cultures entered the stationary phase and during the stationary phase, activity dropped dramatically, eventually reaching undetectable levels. Stimulation of stationary-phase cells with fresh medium resulted in rapid reestablishment of log phase levels. Two mechanisms, the regulation of thymidylate synthase-specific transcripts and the irreversible inactivation of thymidylate synthase activity, acted in concert to regulate activity levels. These results suggested that thymidylate synthase represents a special subset of yeast proteins whose levels per cell vary quickly and dramatically in response to changes in proliferation rates.