double-time Is a Novel Drosophila Clock Gene that Regulates PERIOD Protein Accumulation

We have isolated three alleles of a novel Drosophila clock gene, double-time ( dbt). Short- ( dbt S ) and long-period ( dbt L ) mutants alter both behavioral rhythmicity and molecular oscillations from previously identified clock genes, period and timeless. A third allele, dbt P , causes pupal letha...

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Bibliographic Details
Published in:Cell 1998-07, Vol.94 (1), p.83-95
Main Authors: Price, Jeffrey L, Blau, Justin, Rothenfluh, Adrian, Abodeely, Marla, Kloss, Brian, Young, Michael W
Format: Article
Language:English
Subjects:
Alleles
Animals
Biological Clocks - genetics
Brain - metabolism
Circadian Rhythm - genetics
Darkness
DNA Transposable Elements
Drosophila - cytology
Drosophila - genetics
Drosophila Proteins
Gene Expression Regulation
Genes, Insect
Insect Proteins - biosynthesis
Insect Proteins - genetics
Insect Proteins - metabolism
Larva
Light
Mutagenesis
Nuclear Proteins - biosynthesis
Period Circadian Proteins
RNA, Messenger - biosynthesis
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Summary:We have isolated three alleles of a novel Drosophila clock gene, double-time ( dbt). Short- ( dbt S ) and long-period ( dbt L ) mutants alter both behavioral rhythmicity and molecular oscillations from previously identified clock genes, period and timeless. A third allele, dbt P , causes pupal lethality and eliminates circadian cycling of per and tim gene products in larvae. In dbt P mutants, PER proteins constitutively accumulate, remain hypophosphorylated, and no longer depend on TIM proteins for their accumulation. We propose that the normal function of DOUBLETIME protein is to reduce the stability and thus the level of accumulation of monomeric PER proteins. This would promote a delay between per/ tim transcription and PER/TIM complex function, which is essential for molecular rhythmicity.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)81224-6