Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau.
Science
; 288(5465): 483-92, 2000 Apr 21.
Article
em En
| MEDLINE
| ID: mdl-10775102
ABSTRACT
The tau mutation is a semidominant autosomal allele that dramatically shortens period length of circadian rhythms in Syrian hamsters. We report the molecular identification of the tau locus using genetically directed representational difference analysis to define a region of conserved synteny in hamsters with both the mouse and human genomes. The tau locus is encoded by casein kinase I epsilon (CKIepsilon), a homolog of the Drosophila circadian gene double-time. In vitro expression and functional studies of wild-type and tau mutant CKIepsilon enzyme reveal that the mutant enzyme has a markedly reduced maximal velocity and autophosphorylation state. In addition, in vitro CKIepsilon can interact with mammalian PERIOD proteins, and the mutant enzyme is deficient in its ability to phosphorylate PERIOD. We conclude that tau is an allele of hamster CKIepsilon and propose a mechanism by which the mutation leads to the observed aberrant circadian phenotype in mutant animals.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Ritmo Circadiano
/
Mutação Puntual
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article