FIGURE 1.

Molecular connections between CRY1, CRY2, and cancer-related pathways. The core clock mechanism involves a transcription-translation feedback loop (TTFL) in which the bHLH-PAS transcription factors CLOCK and BMAL1 drive expression of their own repressors, PERs and CRYs (for a more complete description of the molecular clock, see ref.¹). In the face of growing interest in understanding the mechanistic underpinnings for enhanced cancer risk in people exposed to chronic circadian disruption, several molecular connections between clocks and proteins with established roles in regulating cell growth, DNA repair, and the cellular response to DNA damage have been described. See text for details. Proteins outlined in black exhibit widespread circadian expression at the mRNA level. Brown shading denotes tumor suppressors; bright green shading denotes oncogenes. Substrate receptors for multisubunit E3 ligases are shown in red. Red arrows indicate pathways that lead to ubiquitination and 26S proteasome-mediated degradation. Ub, ubiquitin