Phase response to heat shock as evidence for a timekeeping oscillator in synchronous animal cells

Synchronous animal cells given heat shocks at 0.5-h intervals through an 8.5-h cell cycle display a biphasic pattern of advances and delays in subsequent cell divisions. This phase-response curve to perturbation by heat shock has a period of approximately 4 h and cannot readily be explained by commonly used models of cell cycle traverse. We suggest that this outcome is the consequence of timekeeping by a macromolecular oscillator with limit cycle properties.