double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation

Cell. 1998 Jul 10;94(1):83-95. doi: 10.1016/s0092-8674(00)81224-6.


We have isolated three alleles of a novel Drosophila clock gene, double-time (dbt). Short- (dbtS) and long-period (dbtL) mutants alter both behavioral rhythmicity and molecular oscillations from previously identified clock genes, period and timeless. A third allele, dbtP, causes pupal lethality and eliminates circadian cycling of per and tim gene products in larvae. In dbtP 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Biological Clocks / genetics*
  • Brain / metabolism
  • Circadian Rhythm / genetics*
  • DNA Transposable Elements
  • Darkness
  • 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


  • DNA Transposable Elements
  • Drosophila Proteins
  • Insect Proteins
  • Nuclear Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins
  • RNA, Messenger
  • tim protein, Drosophila