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

The mutation timeless(UL) generates 33 hr rhythms, prolonged nuclear localization 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 per and tim expression. Thus, in the absence of TIM, nuclear PER can function as a potent negative transcriptional regulator. Two additional studies support this role for PER: (1) Drosophila expressing PER that constitutively localizes to nuclei produce dominant behavioral arrhythmicity, and (2) constitutively nuclear PER represses dCLOCk/CYCLE-mediated transcription of per in cultured cells without TIM. Conversion of PER/TIM heterodimers to nuclear PER proteins appears to be required to complete transcriptional repression and terminate each circadian molecular cycle.