CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless

Cell. 1998 May 29;93(5):805-14. doi: 10.1016/s0092-8674(00)81441-5.


We report the identification, characterization, and cloning of another novel Drosophila clock gene, cycle (cyc). Homozygous cyc flies are completely arrhythmic. Heterozygous cyc/+ flies are rhythmic but have altered periods, indicating that the cyc locus has a dosage effect on period. The molecular circadian phenotype of homozygous cyc flies is like homozygous Clk flies presented in the accompanying paper: mutant flies have little or no transcription of the per and tim genes. Cloning of the gene indicates that it also encodes a bHLH-PAS transcription factor and is a Drosophila homolog of the human protein BMAL1. cyc is a nonsense mutation, consistent with its strong loss-of-function phenotype. We propose that the CYC:CLK heterodimer binds to per and tim E boxes and makes a major contribution to the circadian transcription of Drosophila clock genes.

Publication types

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

MeSH terms

  • ARNTL Transcription Factors
  • Amino Acid Sequence
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Behavior, Animal
  • Chromosome Mapping
  • Circadian Rhythm / genetics*
  • Cloning, Molecular
  • Drosophila / genetics*
  • Drosophila Proteins*
  • Gene Dosage
  • Genes, Insect
  • Helix-Loop-Helix Motifs
  • Insect Proteins / biosynthesis*
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / biosynthesis*
  • Period Circadian Proteins
  • Sequence Homology, Amino Acid
  • Trans-Activators / genetics*
  • Transcription Factors / genetics
  • Transcription, Genetic


  • ARNTL Transcription Factors
  • ARNTL protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Drosophila Proteins
  • Insect Proteins
  • Nuclear Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins
  • Trans-Activators
  • Transcription Factors
  • cyc protein, Drosophila
  • tim protein, Drosophila

Associated data

  • GENBANK/AF065473