Restriction Point timing and cell cycle variability – a re-evaluation

The Restriction Point (R) in the mammalian cell cycle is regarded as a critical transition in G1 when cells become committed to enter S phase even in the absence of further growth factor stimulation. Classic time-lapse studies by Zetterberg and Larsson suggested that the acquisition of growth factor independence (i.e. passage of R) occurred very abruptly 3-4 hours after mitosis, with most cell cycle variability arising between R and entry into S phase. However, the cycle times of the post-R cells that continued on to mitosis after serum step-down without perturbation were far less variable than the control cells with which they were compared. A re-analysis of the data, presented here, shows that when the timing of R and entry in mitosis are compared for the same experiments, the curves are superimposable and statistically indistinguishable. This indicates that the data are compatible with the timing of R contributing to much of the overall variability in the cell cycle, contrary to the conclusions of Zetterberg and colleagues.