A TIMELESS-independent function for PERIOD proteins in the Drosophila clock.
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. Light-induced 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.
Rothenfluh
A
A
Laboratory of Genetics and National Science Foundation Science and Technology Center for Biological Timing, The Rockefeller University, New York, New York 10021, USA.
Young
M W
MW
Saez
L
L
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins; D017353:Gene Deletion; D019476:Insect Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D009154:Mutation / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D056950:Period Circadian Proteins; D014158:Transcription, Genetic / Q000502:physiology
D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; C096445:tim protein, Drosophila