Two novel doubletime mutants alter circadian properties and eliminate the delay between RNA and protein in Drosophila

Phosphorylation is an important feature of pacemaker organization in Drosop hila. Genetic and biochemical evidence suggests involvement of the casein k inase I homolog doubletime (dbt) in the Drosophila circadian pacemaker. We have characterized two novel dbt mutants. Both cause a lengthening of behav ioral period and profoundly alter period ( per) and timeless (tim) transcri pt and protein profiles. The PER profile shows a major difference from the wild-type program only during the morning hours, consistent with a prominen t role for DBT during the PER monomer degradation phase. The transcript pro files are delayed, but there is little effect on the protein accumulation p rofiles, resulting in the elimination of the characteristic lag between the mRNA and protein profiles. These results and others indicate that light an d posttranscriptional regulation play major roles in defining the temporal properties of the protein curves and suggest that this lag is unnecessary f or the feedback regulation of per and tim protein on per and tim transcript ion.