The vertebrate circadian clock was thought to be highly localized to specific 
anatomical structures: the mammalian suprachiasmatic nucleus (SCN), and the 
retina and pineal gland in lower vertebrates. However, recent findings in the 
zebrafish, rat and in cultured cells have suggested that the vertebrate 
circadian timing system may in fact be highly distributed, with most if not all 
cells containing a clock. Our understanding of the clock mechanism has 
progressed extensively through the use of mutant screening and forward genetic 
approaches. The first vertebrate clock gene was identified only a few years ago 
in the mouse by such an approach. More recently, using a syntenic comparative 
genetic approach, the molecular basis of the the tau mutation in the hamster was 
determined. The tau gene in the hamster appears to encode casein kinase 1 
epsilon, a protein previously shown to be important for PER protein turnover in 
the Drosophila circadian system. A number of additional clock genes have now 
been described. These proteins appear to play central roles in the 
transcription-translation negative feedback loop responsible for clock function. 
Post-translational modification, protein dimerization and nuclear transport all 
appear to be essential features of how clocks are thought to tick.