A circadian clock nanomachine that runs without transcription or translation

The biochemical basis of circadian timekeeping is best characterized in cyanobacteria. The structures of its key molecular players, KaiA, KaiB, and KaiC are known and these proteins can reconstitute a remarkable circadian oscillation in a test tube. KaiC is rhythmically phosphorylated and its phospho-status is a marker of circadian phase that regulates ATPase activity and the oscillating assembly of a nanomachine. Analyses of the nanomachines have revealed how their timing circuit is ratcheted to be unidirectional and how they stay in synch to ensure a robust oscillator. These insights are likely to elucidate circadian timekeeping in higher organisms, including how transcription and translation could appear to be a core circadian timer when the true pacemaker is an embedded biochemical oscillator.

► A biochemical circadian oscillator can be reconstituted with three proteins and ATP. ► The biochemical oscillator drives a Transcription/Translation Feedback Loop in vivo. ► Activities of the core protein include ATPase, kinase and phospho-transferase. ► Structural insights explain unidirectionality, synchrony, robustness, and entrainment.