Abstract
To identify new components of the Drosophila circadian clock, we screened chemically mutagenized flies for suppressors or enhancers of the long periods characteristic of the period (per) mutant allele per L. We isolated a novel mutant that maps to the rhythm gene timeless (tim). This novel alleletimSL, alters the temporal pattern of per L protein nuclear localization and restores temperature compensation to perL flies. timSL more generally manifests specific interactions with different per alleles. The identification of this first period-altering tim allele provides further evidence that TIM is a major component of the clock, and the allele-specific interactions with PER provide evidence that the PER/TIM heterodimer is a unit of circadian function. Although timSL fails to restore PER-L/TIM temperature insensitivity in yeast, it alters the TIM phosphorylation pattern during the late night. The effects on phosphorylation suggest that timSL functions as a partial bypass suppressor of per L and provide evidence that the TIM phosphorylation program contributes to the circadian timekeeping mechanism.