A TIMELESS-independent function for PERIOD proteins in the Drosophila clock

The mutation timeless(UL) generates 33 hr rhythms, prolonged nuclear locali zation of PERIOD/TIMELESSUL protein complexes, and protracted derepression of period (per) and timeless (tim) transcription. Light-induced elimination of TIMUL from nuclear PER/TIMUL complexes gives strong downregulation of p er and tim expression. Thus, in the absence of TIM, nuclear PER can functio n as a potent negative transcriptional regulator. Two additional studies su pport this role for PER: (1) Drosophila expressing PER that constitutively localizes to nuclei produce dominant behavioral arrhythmicity, and (2) cons titutively nuclear PER represses dCLOCk/CYCLE-mediated transcription of per in cultured cells without TIM. Conversion of PER/TIM heterodimers to nucle ar PER proteins appears to be required to complete transcriptional repressi on and terminate each circadian molecular cycle.