Molecular analysis of zebrafish photolyase/cryptochrome family: two types of cryptochromes present in zebrafish

Background: Cryptochromes (CRY), members of the DNA photolyase/cryptochrome protein family, regulate the circadian clock in animals and plants. Two ty pes of animal CRYs are known, mammalian CRY and Drosophila CRY. Both CRYs p articipate in the regulation of circadian rhythm, but they have different l ight dependencies for their reactions and have different effects on the neg ative feedback loop which generates a circadian oscillation of gene express ion. Mammalian CRYs act as a potent inhibitor of transcriptional activator whose reactions do not depend on light, but Drosophila CRY functions as a l ight-dependent suppressor of transcriptional inhibitor. Results: We cloned seven zebrafish genes that carry members of the DNA phot olyase/cryptochrome protein family; one (6-4)photolyase and six cry genes. A sequence analysis and determination of their in vitro functions showed th at these zebrafish cry genes constitute two groups. One has a high sequence similarity to mammalian cry genes and inhibits CLOCK:BMAL1 mediated transc ription. The other, which has a higher sequence similarity to the Drosophil a cry gene rather than the mammalian cry genes, does not carry transcriptio n inhibitor activity. The expressions of these cry genes oscillate in a cir cadian manner, but their patterns differ. Conclusions: These findings suggest that functionally diverse cry genes are present in zebrafish and each gene has different role in the molecular clo ck.