Intracellular and intercellular processes determine robustness of the circadian clock

Circadian clocks are present in most organisms and provide an adaptive mechanism to coordinate physiology and behavior with predictable changes in the environment. Genetic, biochemical, and cellular experiments have identified more than a dozen component genes and a signal transduction pathway that support cell-autonomous, circadian clock function. One of the hallmarks of biological clocks is their ability to reset to relevant stimuli while ignoring most others. We review recent results showing intracellular and intercellular mechanisms that convey this robust timekeeping to a variety of circadian cell types.

► Circadian systems oscillate in a noisy environment and entrain to daily timing cues.
► Their robustness against environmental and genetic perturbations depends on their biochemical and genetic architecture.
► Paralog compensation, transcriptional response programs and balanced biochemical feedback loops help sustain daily cycling.
► Robustness also arises from intercellular (e.g. neurotransmission) and systems-level signals (e.g. body temperature).