The molecular control of circadian behavioral rhythms and their entrainment in Drosophila.

Molecular and genetic characterizations of circadian rhythms in Drosophila indicate that function of an intracellular pacemaker requires the activities of proteins encoded by three genes: period (per), timeless (tim), and doubletime (dbt). RNA from two of these genes, per and tim, is expressed with a circadian rhythm. Heterodimerization of PER and TIM proteins allows nuclear localization and suppression of further RNA synthesis by a PER/TIM complex. These protein interactions promote cyclical gene expression because heterodimers are observed only at high concentrations of per and tim RNA, separating intervals of RNA accumulation from times of PER/TIM complex activity. Light resets these molecular cycles by eliminating TIM. The product of dbt also regulates accumulation of per and tim RNA, and it may influence action of the PER/TIM complex. The recent discovery of PER homologues in mice and humans suggests that a related mechanism controls mammalian circadian behavioral rhythms.