Cryptochromes nucleus

The mammalian molecular oscillator, similar to that in Drosophila and Neurospora, is composed of two interconnected feedback loops, one within the negative limb and one within the positive limb. The members of the positive limb (CLOCK and BMALl) activate transcription of the genes encoding the negative limb components (cryptochromes and period proteins). PER and CRY proteins then form heterotypic protein complexes that are translocated into the nucleus, and once these complexes reach a critical threshold level, they suppress the activity of CLOCK and BMALL As a consequence, the concentration of CRY and PER proteins falls below the threshold required for autorepression, and a new cycle of CryjPer transcription can initiate (for review, see Reppert Weaver 2002). 

Kara R, Wan K, Wakamatsu H et al 2001 Restricted feeding entrains liver clock without participation of the suprachiasmatic nucleus. Genes Cells 6 269—278 Selby CP, Thompson C, Schmitz TM, Van Gelder RN, Sancar A 2000 Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc Natl Acad Sci USA 97 14697-14702... 

Cryptochromes in the human eye have a considerable sequence and structure homology with the photolyases, binding both methylene tetrahydrofolate and FAD. They have the same DNA binding pocket as photolyase, although they do not catalyze the reduction of DNA pyrimidine dimers. They are found in the nucleus of cells of the inner layer of the retina, behind the rods and cones involved in vision (Section 2.3.1), and absorb blue light, with maximum absorbance at 420 nm. 

Cryptochrome genes have been found in many organisms. In the fly Drosophila cryptochrome appears to interact directly with the clock proteins that control the circadian cycle. Most important are products of two genes per (period) and tim (timeless). They are helix-loop-helix DNA binding proteins that form heterodimers, are translocated to the nucleus, and repress their own transcription. Morning light leads to a rapid disappearance of e TIM protein. The cryptochrome CRY appears to react directly with TIM to inactivate it. However, details remain to be learned. " The circadian clock mechanism appears to be universal and the cryptochrome-2 mcryl gene) appears to function in the mouse. A human cDNA clone was found to have a 48% identity with a relative of cryptochromes, the (6-4) photolyase of Drosophila. 

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