Quasi-exponential generation time distributions from a limit cycle oscillator.

In spite of the apparently random behaviour and the often exponential distribution of generation times expressed in cell populations, there is evidence for rather precise timekeeping in the cell cycle. In experiments using time-lapse video-tape microscopy, we have noted that cell generation times are often not distributed smoothly but in many cases seem to cluster at roughly 4 hr intervals. Phase shift responses following application of heat shock, ionizing radiation or serum pulses in each case show a pattern which is repeated twice in cells with an 8-9 hr modal generation time. We describe here a cell cycle model with an independent cellular clock controlling cell cycle events which accounts for the phase response data, while also reconciling the stochastic and periodic behaviour characteristic of animal cells.