Circadian rhythms are oscillations in the biochemical, physiological, and behavioral functions of organisms that occur with a periodicity of approximately 24 h. They are generated by a molecular clock that is synchronized with the solar day by environmental photic input. The cryptochromes are the mammalian circadian photoreceptors. They absorb light and transmit the electromagnetic signal to the molecular clock using a pterin and flavin adenine dinucleotide (FAD) as chromophore/cofactors, and are evolutionarily conserved and structurally related to the DNA repair enzyme photolyase. Humans and mice have two cryptochrome genes, and , that are differentially expressed in the retina relative to the opsin-based visual photoreceptors. is highly expressed with circadian periodicity in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN). Mutant mice lacking either or have impaired light induction of the clock gene and have abnormally short or long intrinsic periods, respectively. The double mutant has normal vision but is defective in induction by light and lacks molecular and behavioral rhythmicity in constant darkness. Thus, cryptochromes are photoreceptors and central components of the molecular clock. Genetic evidence also shows that cryptochromes are circadian photoreceptors in and , raising the possibility that they may be universal circadian photoreceptors. Research on cryptochromes may provide new understanding of human diseases such as seasonal affective disorder and delayed sleep phase syndrome.


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