LIGHT-INDUCED RESETTING OF A CIRCADIAN CLOCK IS MEDIATED BY A RAPID INCREASE IN FREQUENCY TRANSCRIPT

To understand how light entrains circadian clocks, we examined the eff ects of light on a gene known to encode a state variable of a circadia n oscillator, the frequency (frq) gene, fro is rapidly induced by shor t pulses of visible light; clock resetting is correlated with fro indu ction and is blocked by drugs that block the synthesis of protein or t ranslatable RNA. The speed and magnitude of fro induction suggest that this may be the initial clock-specific event in light resetting. Ligh t induction overcomes fro negative autoregulation so that frq expressi on can remain high in constant light. These data explain how a simple unidirectional signal (light and the induction of frq) may be turned i nto a bidirectional clock response (time of day-specific advances and delays). This light entrainment model is easily generalized and may be the common mechanism by which the intracellular feedback cycles that comprise circadian clacks are brought into synchrony with external cyc les in the real world.