title: Positional cloning of the mouse circadian clock gene.
abstract: We used positional cloning to identify the circadian Clock gene in mice. Clock is a large transcription unit with 24 exons spanning approximately 100,000 bp of DNA from which transcript classes of 7.5 and approximately 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.
authors.affiliation: National Science Foundation Center for Biological Timing, Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: King
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: A M
authors.initials: AM
authors.lastname: Sangoram
authors.forename: L D
authors.initials: LD
authors.lastname: Wilsbacher
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: M P
authors.initials: MP
authors.lastname: Antoch
authors.forename: T D
authors.initials: TD
authors.lastname: Steeves
authors.forename: M H
authors.initials: MH
authors.lastname: Vitaterna
authors.forename: J M
authors.initials: JM
authors.lastname: Kornhauser
authors.forename: P L
authors.initials: PL
authors.lastname: Lowrey
authors.forename: F W
authors.initials: FW
authors.lastname: Turek
authors.forename: J S
authors.initials: JS
authors.lastname: Takahashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D056926:CLOCK Proteins; D002642:Chick Embryo; D002874:Chromosome Mapping; D002940:Circadian Rhythm / Q000235:genetics*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs; D004330:Drosophila / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D015534:Trans-Activators; D056926:CLOCK Proteins; C538943:CLOCK protein, human; C538944:Clock protein, mouse