THE DROSOPHILA CLOCK GENE DOUBLE-TIME ENCODES A PROTEIN CLOSELY-RELATED TO HUMAN CASEIN KINASE-I-EPSILON

The cloning of double-time (dbt) is reported. DOUBLETIME protein (DBT) is most closely related to human casein kinase le. dbt(s) and dbt(L) mutations, which alter period length of Drosophila circadian rhythms, produce single amino acid changes in conserved regions of the predicte d kinase. dbf(P) mutants, which eliminate rhythms of per and tim expre ssion and constitutively overproduce hypophosphorylated PER proteins, abolish most dbt expression. dbt mRNA appears to be expressed in the s ame cell types as are per and tim and shows no evident oscillation in wild-type heads. DBT is capable of binding to PER in vitro and in Dros ophila cells, suggesting that a physical association of PER and DBT re gulates PER phosphorylation and accumulation in vivo.