THE DROSOPHILA CLOCK PROTEIN UNDERGOES DAILY RHYTHMS IN ABUNDANCE, PHOSPHORYLATION, AND INTERACTIONS WITH THE PER-TIM COMPLEX

We report the in vivo characterization of the Drosophila CLOCK protein (dCLOCK), a transcription factor that is required for the expression of the circadian clock genes period (per) and timeless (tim). dCLOCK u ndergoes circadian fluctuations in abundance, is phosphorylated throug hout a daily cycle, and interacts with PER, TIM, and/or the PER-TIM co mplex during the night but not during most of the day. Our results sug gest that PER and TIM participate in transcriptional autoinhibition by physically interacting with dCLOCK or a dCLOCK-containing complex. Ne vertheless, in the absence of PER or TIM, the levels of dCLOCK are con stitutively low, indicating that PER and TIM also act as positive elem ents in the feedback loop by stimulating the production of dCLOCK.