TY - JOUR
T1 - Short-period mutations of per affect a double-time-dependent step in the Drosophila circadian clock
AU - Rothenfluh, Adrian
AU - Abodeely, Marla
AU - Young, Michael W.
N1 - Funding Information:
We thank Ralf Stanewsky and Jeff Hall for anti-PER antibody, Vipin Suri and Michael Rosbash for communicating data prior to publication, and Doug Guarnieri, Aylin Rodan and especially Justin Blau for critical reading of the manuscript. A.R. was supported by a Beckman fellowship. This work was funded by NIH GM 54339, and the NSF Science and Technology Center for Biological Timing (M.W.Y.).
PY - 2000/11/2
Y1 - 2000/11/2
N2 - Circadian (24 hour) PERIOD (PER) protein oscillation is dependent on the double-time (dbt) gene, a casein kinase lε 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 lε 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.
AB - Circadian (24 hour) PERIOD (PER) protein oscillation is dependent on the double-time (dbt) gene, a casein kinase lε 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 lε 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.
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U2 - 10.1016/S0960-9822(00)00786-7
DO - 10.1016/S0960-9822(00)00786-7
M3 - Article
C2 - 11084344
AN - SCOPUS:0034597629
SN - 0960-9822
VL - 10
SP - 1399
EP - 1402
JO - Current Biology
JF - Current Biology
IS - 21
ER -