A TIMELESS-Independent Function for PERIOD Proteins in the Drosophila Clock

• Published in: Neuron (Cambridge, Mass.) Vol. 26; no. 2; pp. 505 - 514
• Main Authors: Rothenfluh, Adrian, Young, Michael W., Saez, Lino
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2000
• Subjects: Animals; Biological Clocks - physiology; Cell Line; Cell Nucleus - metabolism; Circadian Rhythm - physiology; dCLOCK/CYCLE protein; Drosophila; Drosophila - physiology; Drosophila Proteins; Gene Deletion; Insect Proteins - genetics; Insect Proteins - isolation & purification; Insect Proteins - metabolism; Insect Proteins - physiology; Mutation - physiology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nuclear Proteins - physiology; period (per) gene; Period Circadian Proteins; period gene; PERIOD protein; timeless (tim) gene; timeless gene; TIMELESS protein; Transcription, Genetic - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)81182-4

The mutation
timeless
UL
generates 33 hr rhythms, prolonged nuclear localization of PERIOD/TIMELESS
UL protein complexes, and protracted derepression of
period (
per) and
timeless (
tim) transcription. Lightinduced elimination of TIM
UL from nuclear PER/TIM
UL 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.