Entrainment of the Mammalian Cell Cycle by the Circadian Clock: Modeling Two Coupled Cellular Rhythms
Figure 5
Entrainment of the cell cycle to 24 h or 48 h.
The cell cycle is coupled to the circadian clock through the kinase Wee1. Shown in each panel are the time series for cyclin B/Cdk1 (red), the kinase Wee1 (blue) and the circadian complex CLOCK-BMAL1 (green) before (t<120 h) or after (t>120 h) coupling to the circadian clock. Conditions A–C correspond, respectively, to points A–C in Fig. 4A. (A) The cell cycle has an autonomous period of 16 h and is entrained to 24 h when the coupling strength, measured by parameter vsw is sufficiently large. In t = 120 h, vsw is raised from 0 to 0.02 µM h−1. (B) For the same coupling strength, i.e. for the same increase in vsw, entrainment to 48 h occurs when the autonomous period prior to coupling is 38 h. One peak in Cdk1 occurs for every second peak in BMAL1. (C) When the autonomous period is 16 h as in (A), the cell cycle fails to be entrained by the circadian clock when the coupling strength is reduced; here vsw increases from 0 to 0.0012 µM h−1 in t = 120 h. Other parameters values are the same as in Fig. 4A.