A Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback Regulation in Limiting Cellular Variability
Fig 7
Positive feedback in SIC1 degradation and CLB2 activation.
A and B. Temporal dynamics of total Sic1 are plotted for three WT and three clb5Δclb6Δ cells in glucose medium (μ = 0.007 min−1). The solid red lines fit the decay of Sic1 to a single exponential function to obtain the timescale of Sic1 degradation in individual cells. C. Half-lives of Sic1 in individual cells are clustered for WT and various mutant cells, showing that the deletion of S phase cyclin genes (CLB5 and CLB6 but not CLN1 and CLN2) increases the average half-life and the variability of Sic1 degradation, causing an increase in the delay time and the variability of the onset of DNA synthesis (Tg1) (inset). D and E. The durations of SG2M phase (Tsg2m = Tdiv−Tg1) from single-cycle simulations of an extant population of daughter and mother cells are plotted for WT cells, WT cells with decreased rate constant for the phosphorylation of Fkh2 by Clb2 (i.e., decreasing strength of the positive feedback for CLB2 activation), and WT cells with the weakest positive feedback loop and increased rate constants for phosphorylation of Fkh2 by Cln1,2,3 and Clb5. In each plot, the horizontal red line represents the median, the blue box represents 25th to 75th percentile of data, the horizontal black lines represent edges of data points and outliers are plotted as red dots. F and G. The average and CV of Tsg2m are plotted for the data in D and E.