Short-period mutations of per affect a double-time-dependent step in the Drosophila circadian clock.
Circadian (24 hour) PERIOD (PER) protein oscillation is dependent on the double-time (dbt) gene, a casein kinase Ivarepsilon homolog [1-3]. Without dbt activity, hypophosphorylated PER proteins over-accumulate, indicating that dbt is required for PER phosphorylation and turnover [3,4]. There is evidence of a similar role for casein kinase Ivarepsilon in the mammalian circadian clock [5,6]. We have isolated a new dbt allele, dbt(ar), which causes arrhythmic locomotor activity in homozygous viable adults, as well as molecular arrhythmicity, with constitutively high levels of PER proteins, and low levels of TIMELESS (TIM) proteins. Short-period mutations of per, but not of tim, restore rhythmicity to dbt(ar) flies. This suppression is accompanied by a restoration of PER protein oscillations. Our results suggest that short-period per mutations, and mutations of dbt, affect the same molecular step that controls nuclear PER turnover. We conclude that, in wild-type flies, the previously defined PER'short domain' [7,8] may regulate the activity of DBT on PER.
Rothenfluh
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A
Laboratory of Genetics, and National Science Foundation Science and Technology Center for Biological Timing, The Rockefeller University, New York, New York 10021, USA.
Abodeely
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Young
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D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D048149:Casein Kinase 1 epsilon; D002940:Circadian Rhythm; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000502:physiology*; D005838:Genotype; D019476:Insect Proteins / Q000378:metabolism; D009043:Motor Activity; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins; D010766:Phosphorylation; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism
D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; C113519:dco protein, Drosophila; C096445:tim protein, Drosophila; D011494:Protein Kinases; D048149:Casein Kinase 1 epsilon