The tim(SL) mutant of the Drosophila rhythm gene timeless manifests allele-specific interactions with period gene mutants

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 Goer) mutant allele per(L). We isolated a novel mutant that maps to the rhythm gene timeless (fim). This novel allele, tim(SL), alters the temporal pattern of per(L) protein nuclear localization and restores temperature compensation to per(L) flies. tim(SL) 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 tim(SL) 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 tim(SL) functions as a partial bypass suppressor of per(L) and provide evidence that the TIM phosphorylation program contributes to the circadian timekeeping mechanism.