CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping

摘要: Circadian (approximately daily) rhythms are a pervasive property of mammalian cells, tissues, and behaviour, ensuring physiological metabolic adaptation to solar time. Models daily cellular timekeeping revolve around transcriptional feedback repression, whereby CLOCK BMAL1 activate the expression clock proteins PERIOD (PER) CRYPTOCHROME (CRY), which in turn repress CLOCK/BMAL1 activity. CRY thus considered essential negative regulators oscillation; function supported by behavioural arrhythmicity CRY-deficient mice when kept under constant conditions. Challenging this interpretation, however, we find evidence for persistent circadian mouse behaviour PER2 levels is absent. CRY-less oscillations variable their have shorter period than wild type controls. Importantly, classic hallmarks such as temperature compensation determination casein kinase 1d/e; activity be maintained. In absence CRY-mediated repression rhythmic Per2 transcription, protein sustained several cycles, accompanied variation stability. We suggest that, whereas imparts robustness functionality onto biological clocks, core mechanism post-translational. Our findings that PER normally act signalling hubs transduce timing information nucleus, imparting upon effectors.