Biological timekeeping is determined by internal temporal programmes and the resetting of these programmes or clocks by external stimuli. Many of the core genes of the mammalian daily or circadian clock are known, but the factors regulating so-called ‘clock’ gene proteins are unclear. In this issue of the Biochemical Journal, Gallego and colleagues show for the first time that protein phosphatase 1 plays a major role in the stability of mammalian PER2, a key protein in the core clock works. This contrasts somewhat with circadian rhythm control in the fruitfly Drosophila and the fungus Neurospora where current evidence supports a role for protein phosphatase 2A in core timekeeping. The mechanisms underpinning these actions of phosphatase 1 are unclear, and future investigations will need to identify the regulatory subunit that targets phosphatase 1 to mammalian PER2 (Period 2).

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