CYCLE IS A 2ND BHLH-PAS CLOCK PROTEIN ESSENTIAL FOR CIRCADIAN RHYTHMICITY AND TRANSCRIPTION OF DROSOPHILA PERIOD AND TIMELESS

We report the identification, characterization, and cloning of another novel Drosophila clock gene, cycle (cyc). Homozygous cyc flies are co mpletely arrhythmic. Heterozygous cyc/+ flies are rhythmic but have al tered periods, indicating that the cyc locus has a dosage effect on pe riod. The molecular circadian phenotype of homozygous cyc flies is lik e homozygous Clk flies presented in the accompanying paper: mutant fli es have little or no transcription of the per and tim genes. Cloning o f the gene indicates that it also encodes a bHLH-PAS transcription fac tor and is a Drosophila homolog of the human protein BMAL1. cyc is a n onsense mutation, consistent with its strong loss-of-function phenotyp e. We propose that the CYC:CLK heterodimer binds to per and tim E boxe s and makes a major contribution to the circadian transcription of Dro sophila clock genes.