Entrainment of the Mammalian Cell Cycle by the Circadian Clock: Modeling Two Coupled Cellular Rhythms
Figure 3
Phase of the cell cycle in the light-dark (LD) cycle upon entrainment by the circadian clock through the kinase Wee1.
The time series show the time evolution of cyclin B/Cdk1 and of Wee1 mRNA in the absence (vsw = 0 for t<120 h) or presence (vsw = 0.1 µM h−1 for t>120 h) of coupling to the circadian clock, when the autonomous period of the cell cycle, prior to coupling via Wee1, is smaller (20 h, A) or larger (28 h, B) than 24 h. In both cases, cyclin B/Cdk1 peaks at the end of the L phase upon entrainment, in agreement with experimental observations [23]. The square wave (dashed line) represents the 24-h LD cycle; it corresponds to the increase above a basal value in the rate of synthesis, vsP, of Per mRNA during the L phase. This increment goes from zero in the D phase to 0.3 nM h−1 in the L phase. In all figures the durations of the L and D phases are equal to 16 h and 8 h, respectively. The values of the parameters in the model for the circadian clock are those corresponding to Fig. 8 of the Supporting Information in [21], with Kib = 1 nM. The desired autonomous period of the cell cycle is achieved by adjusting the scaling parameter eps (see [14] and Methods), with eps = 21.58 in A, and 15.37 in B. Parameter values are the same as in Fig. 2.