title: CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless.
abstract: 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.
authors.affiliation: NSF, Center for Biological Timing, and Department of Biology, Brandeis University, Waltham, Massachusetts 02254, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Rutila
authors.forename: V
authors.initials: V
authors.lastname: Suri
authors.forename: M
authors.initials: M
authors.lastname: Le
authors.forename: W V
authors.initials: WV
authors.lastname: So
authors.forename: M
authors.initials: M
authors.lastname: Rosbash
authors.forename: J C
authors.initials: JC
authors.lastname: Hall
mesh_terms: D056930:ARNTL Transcription Factors; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001522:Behavior, Animal; D002874:Chromosome Mapping; D002940:Circadian Rhythm / Q000235:genetics*; D003001:Cloning, Molecular; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D018628:Gene Dosage; D017344:Genes, Insect; D018257:Helix-Loop-Helix Motifs; D019476:Insect Proteins / Q000096:biosynthesis*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000096:biosynthesis*; D056950:Period Circadian Proteins; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C538960:BMAL1 protein, human; C539040:PER protein, Drosophila; C112805:cyc protein, Drosophila; C096445:tim protein, Drosophila