Double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation

We have isolated three alleles of a novel Drosophila clock gene, double-time (dbt). Short- (dbts) and long-period (dbt(L)) mutants after both behavioral rhythmicity and molecular oscillations from previously identified clock genes, period and timeless. A third allele, dbf(P), causes pupal lethality and eliminates circadian cycling of per and tim gene products in larvae. In dbt(P) mutants, PER proteins constitutively accumulate, remain hypophosphorylated, and no longer depend on TIM proteins for their accumulation. We propose that the normal function of DOUBLETIME protein is to reduce the stability and thus the level of accumulation of monomeric PER proteins. This would promote a delay between per/tim transcription and PER/TIM complex function, which is essential for molecular rhythmicity.