Casein kinase 1 and disordered clock proteins form functionally equivalent, phospho-based circadian modules in fungi and mammals

Abstract

Significance Circadian clocks rely on negative feedback loops. The core circadian inhibitors, FRQ in Neurospora and PERs in animals, are progressively hyperphosphorylated, inactivated, and degraded. CK1 is essential for these clocks. Despite our knowledge of the role of CK1, it is not known how many other kinases are required and how multisite phosphorylation might contribute to circadian timekeeping. We show here that CK1 alone is sufficient to slowly phosphorylate low-affinity sites in FRQ or PER2. The reaction is nearly temperature compensated, and the phosphorylation state of FRQ or PER2 corresponds to the time elapsed since the start of the reaction. Thus, CK1 and FRQ or PER2 form equivalent modules that are in principle capable of measuring time on a circadian scale.