Figure 3. Roles of CRY outside of CLOCK:BMAL1 regulation.

In mammals, CRYs negatively regulate CLOCK:BMAL1 activity to generate a ~24 hour clock that regulates ~40% of the genome (88). CRY is also reported to regulate GPCR signaling and downstream metabolism through interaction with the G_sα subunit to block glucagon-stimulated increases in intracellular cAMP (top left). CRY negatively regulates the glucocorticoid receptor to maintain glucose homeostasis, partly through regulation of Pck1 expression (top right). Interaction of CRY with components of the ATR-mediated DNA damage checkpoint control phase shifting of the clock in response to DNA damage (bottom left). While ablation of the SCN increases tumor formation in mouse models, deletion of cryptochromes extends lifespan after ionizing radiation in a p53 null background (bottom right).