title: A role for the PERIOD:PERIOD homodimer in the Drosophila circadian clock.
abstract: Circadian clocks in eukaryotes rely on transcriptional feedback loops, in which clock genes repress their own transcription resulting in molecular oscillations with a period of approximately 24 h. In Drosophila, the clock proteins Period (PER) and Timeless (TIM) operate in such a feedback loop, whereby they first accumulate in the cytoplasm of clock cells as a heterodimer. Nuclear translocation of the complex or the individual PER and TIM proteins is followed by repression of per and tim transcription, whereby PER seems to act as the prime repressor. We found that in addition to PER:TIM complexes, functional PER:PER homodimers exist in flies. Specific disruption of PER homodimers results in drastically impaired behavioral and molecular rhythmicity, pointing the biological importance of this clock protein complex. Analysis of PER subcellular distribution and repressor competence in the PER dimer mutant revealed defects in PER nuclear translocation and a disruption of rhythmic period transcription. The striking similarity of these phenotypes with that of reduced CKII activity suggests that the formation or function of the PER dimer is closely linked to this kinase. Our results confirm a previous structural model for PER and provide strong evidence that PER homodimers are important for circadian clock function.
authors.affiliation: Institut für Zoologie, Universität Regensburg, Regensburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Landskron
authors.forename: Ko Fan
authors.initials: KF
authors.lastname: Chen
authors.forename: Eva
authors.initials: E
authors.lastname: Wolf
authors.forename: Ralf
authors.initials: R
authors.lastname: Stanewsky
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000235:genetics; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D017344:Genes, Insect; D008124:Locomotion / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins; D055503:Protein Multimerization / Q000235:genetics; D017433:Protein Structure, Secondary
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; C096445:tim protein, Drosophila; D047390:Casein Kinase II