Rutila J E, Suri V, Le M, So W V, Rosbash M, Hall J C
NSF, Center for Biological Timing, and Department of Biology, Brandeis University, Waltham, Massachusetts 02254, USA.
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.
我们报告了另一个新的果蝇生物钟基因——周期基因（cyc）的鉴定、特性分析及克隆。纯合的cyc果蝇完全没有节律。杂合的cyc/+果蝇有节律，但周期发生了改变，这表明cyc基因座对周期有剂量效应。纯合cyc果蝇的分子昼夜节律表型与随附论文中呈现的纯合Clk果蝇相似：突变果蝇的per和tim基因几乎没有转录或完全不转录。该基因的克隆表明它也编码一种bHLH-PAS转录因子，并且是人类蛋白质BMAL1的果蝇同源物。cyc是一个无义突变，与其强大的功能丧失表型一致。我们提出CYC:CLK异源二聚体与per和tim基因的E盒结合，并对果蝇生物钟基因的昼夜节律转录起主要作用。
