Phosphorylation of PERIOD is influenced by cycling physical associations of DOUBLE-TIME, PERIOD, and TIMELESS in the Drosophila clock

The clock gene double-time (dbt) encodes an ortholog of casein kinase le th at promotes phosphorylation and turnover of the PERIOD protein. Whereas the period (per), timeless (tim), and dClock (dClk) genes of Drosophila each c ontribute cycling mRNA and protein to a circadian clock, dbt RNA and DBT pr otein are constitutively expressed. Robust circadian changes in DBT subcell ular localization are nevertheless observed in clock-containing cells of th e fly head. These localization rhythms accompany formation of protein compl exes that include PER, TIM, and DBT, and reflect periodic redistribution be tween the nucleus and the cytoplasm. Nuclear phosphorylation of PER is stro ngly enhanced when TIM is removed from PER/TIM/DBT complexes. The varying a ssociations of PER, DBT and TIM appear to determine the onset and duration of nuclear PER function within the Drosophila clock.