Positional cloning of the mouse circadian Clock gene

David P. King, Yaliang Zhao, Ashvin M. Sangoram, Lisa D. Wilsbacher, Minoru Tanaka, Marina P. Antoch, Thomas D L Steeves, Martha Hotz Vitaterna, Jon M. Kornhauser, Phillip L. Lowrey, Fred W. Turek, Joseph S. Takahashi

Research output: Contribution to journalArticlepeer-review

1085 Scopus citations

Abstract

We used positional cloning to identify the circadian Clock gene in mice. Clock is a large transcription unit with 24 exons spanning ~100,000 bp of DNA from which transcript classes of 7.5 and ~10 kb arise. Clock encodes a novel member of the bHLH-PAS family of transcription factors. In the Clock mutant allele, an A→T nucleotide transversion in a splice donor site causes exon skipping and deletion of 51 amino acids in the CLOCK protein. Clock is a unique gene with known circadian function and with features predicting DNA binding, protein 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 conserved feature of the circadian clock mechanism.

Original languageEnglish (US)
Pages (from-to)641-653
Number of pages13
JournalCell
Volume89
Issue number4
DOIs
StatePublished - May 16 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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