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Summary
Your alarm clock rings in the morning—it's time to get up, but you feel like it's the middle of the night. If this is happening regularly, your circadian clock may not be adjusted to your social life. Circadian clocks are endogenous oscillators that coordinate not only our sleep-wake behavior with the environmental 24-hour light-dark cycle but also a myriad of rhythmic physiological and metabolic processes. A set of so-called clock genes comprises a regulatory network that generates self-sustained molecular ~24-hour rhythms of gene expression. For eukaryotic clocks, the prevailing conceptual model proposes a negative transcriptional-translational feedback loop (1). On page 518 of this issue, Larrondo et al. (2) challenge the molecular basis of this view.