title: Circadian rhythms. Decoupling circadian clock protein turnover from circadian period determination.
abstract: The mechanistic basis of eukaryotic circadian oscillators in model systems as diverse as Neurospora, Drosophila, and mammalian cells is thought to be a transcription-and-translation-based negative feedback loop, wherein progressive and controlled phosphorylation of one or more negative elements ultimately elicits their own proteasome-mediated degradation, thereby releasing negative feedback and determining circadian period length. The Neurospora crassa circadian negative element FREQUENCY (FRQ) exemplifies such proteins; it is progressively phosphorylated at more than 100 sites, and strains bearing alleles of frq with anomalous phosphorylation display abnormal stability of FRQ that is well correlated with altered periods or apparent arrhythmicity. Unexpectedly, we unveiled normal circadian oscillations that reflect the allelic state of frq but that persist in the absence of typical degradation of FRQ. This manifest uncoupling of negative element turnover from circadian period length determination is not consistent with the consensus eukaryotic circadian model.
authors: Millennium Nucleus for Fungal Integrative and Synthetic Biology, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile. Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. jay.c.dunlap@dartmouth.edu llarrondo@bio.puc.cl.
authors: Luis F
authors: LF
authors: Larrondo
authors: Millennium Nucleus for Fungal Integrative and Synthetic Biology, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.
authors: Consuelo
authors: C
authors: Olivares-Yañez
authors: Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors: Christopher L
authors: CL
authors: Baker
authors: Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors: Jennifer J
authors: JJ
authors: Loros
authors: Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. jay.c.dunlap@dartmouth.edu llarrondo@bio.puc.cl.
authors: Jay C
authors: JC
authors: Dunlap
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000483:Alleles; D057906:Circadian Clocks; D002940:Circadian Rhythm; D025461:Feedback, Physiological; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D006207:Half-Life; D009492:Neurospora crassa / Q000502:physiology*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D055550:Protein Stability; D059748:Proteolysis; D015398:Signal Transduction
chemical_list: C087405:FRQ protein, Neurospora crassa; D005656:Fungal Proteins; D047428:Protein Kinase Inhibitors; C001020:N(6),N(6)-dimethyladenine; D046988:Proteasome Endopeptidase Complex; D000225:Adenine
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