Positional cloning of the mouse circadian Clock gene

被引:1124
作者
King, DP [1 ]
Zhao, YL [1 ]
Sangoram, AM [1 ]
Wilsbacher, LD [1 ]
Tanaka, M [1 ]
Antoch, MP [1 ]
Steeves, TDL [1 ]
Vitaterna, MH [1 ]
Kornhauser, JM [1 ]
Lowrey, PL [1 ]
Turek, FW [1 ]
Takahashi, JS [1 ]
机构
[1] NORTHWESTERN UNIV, DEPT NEUROBIOL & PHYSIOL, NATL SCI FDN CTR BIOL TIMING, EVANSTON, IL 60208 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
D O I
10.1016/S0092-8674(00)80245-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We used positional cloning to identify the circadian Clock gene in mice. 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 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.
引用
收藏
页码:641 / 653
页数:13
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