Regulation of the Mammalian Circadian Clock by Cryptochrome

Photolyase/cryptochrome blue-light photoreceptors are monomeric proteins of 50–70 kDa that contain two non-covalently bound chromophore/cofactors (1, 2). One of the cofactors is always FAD. The second chromophore is methenyltetrahydrofolate (MTHF)1 in most organisms and 8-hydroxy-5-deazariboflavin in a few species that synthesize this cofactor. Photolyase repairs UV-induced DNA damage using violet/blue light (350–500 nm) as the energy source to initiate the reaction. Cryptochrome, which exhibits up to 50% sequence identity to some photolyases (3), regulates some of the blue-light responses including growth and development in plants and the circadian rhythm by light-independent and light-dependent mechanisms in animals (4, 5).