CYCLE Is a Second bHLH-PAS Clock Protein Essential for Circadian Rhythmicity and Transcription of Drosophila period and timeless

Homozygous cyc flies are completely arrhythmic.

• Heterozygous cyc/+ flies exhibit rhythmic behavior with altered periods, suggesting a dosage effect of the cyc gene on circadian rhythms.
• The molecular characteristics of homozygous cyc flies are similar to those of homozygous Clk flies, showing minimal transcription of the per and tim genes.
• Cloning of the cyc gene reveals it encodes a bHLH-PAS transcription factor, identified as a Drosophila homolog of the human protein BMAL1.
• The cyc mutation is a nonsense mutation, correlating with its significant loss-of-function effects.
• The CYC:CLK protein complex may play a key role in regulating the transcription of Drosophila clock genes.

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