A clockwork organ

The vertebrate circadian clock was thought to be highly localized to specif ic 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 vertebr ate 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 vert ebrate 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 pr otein previously shown to be important for PER protein turnover in the Dros ophila circadian system. A number of additional clock genes have now been d escribed. These proteins appear to play central roles in the transcription- translation negative feedback loop responsible for clock function. Post-tra nslational modification, protein dimerization and nuclear transport all app ear to be essential features of how clocks are thought to tick.