Figure 1.

Core circadian clock network. The core molecular clock machinery is encoded by a transcription-translation feedback loop that oscillates with a ∼24 hour periodicity. The bHLH-PAS transcription factors CLOCK and BMAL1 heterodimerize to drive expression of downstream target genes containing E-box sequences. Among these, the period (PER) and cryptochrome (CRY) proteins become phosphorylated by CKIepsilon/delta, multimerize and inhibit the action of the CLOCK:BMAL1 complex. The NAD⁺-dependent deacetylase SIRT1 comprises a recently discovered regulatory clock feedback loop.