POSITIONAL CLONING OF THE MOUSE CIRCADIAN CLOCK GENE

We used positional cloning to identify the circadian Clock gene in mic e. Clock is a large transcription unit with 24 exons spanning similar to 100,000 bp of DNA from which transcript classes of 7.5 and similar to 10 kb arise. Clock encodes a novel member of the bHLH-PAS family of transcription factors. In the Clock mutant allele, an A-->T nucleotid e transversion in a splice donor site causes exon skipping and deletio n of 51 amino acids in the CLOCK protein. Clock is a unique gene with known circadian function and with features predicting DNA binding, pro tein dimerization, and activation domains. CLOCK represents the second example of a PAS domain-containing clock protein (besides Drosophila PERIOD), which suggests that this motif may define an evolutionarily c onserved feature of the circadian clock mechanism.