Rutila, J.E., Suri, V., Le, M., So, W.V., Rosbash, M., Hall, J.C. (1998). CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless.  Cell 93(5): 805--814.

FBrf0102728

Research paper

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.