Je. Rutila et al., THE TIM(SL) MUTANT OF THE DROSOPHILA RHYTHM GENE TIMELESS MANIFESTS ALLELE-SPECIFIC INTERACTIONS WITH PERIOD GENE MUTANTS, Neuron, 17(5), 1996, pp. 921-929
To identify new components of the Drosophila circadian clock, we scree
ned chemically mutagenized flies for suppressors or enhancers of the l
ong periods characteristic of the period Goer) mutant allele per(L). W
e isolated a novel mutant that maps to the rhythm gene timeless (fim).
This novel allele, tim(SL), alters the temporal pattern of per(L) pro
tein 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-alteri
ng tim allele provides further evidence that TIM is a major component
of the clock, and the allele-specific interactions with PER provide ev
idence that the PER/TIM heterodimer is a unit of circadian function. A
lthough tim(SL) fails to restore PER-L/TIM temperature insensitivity i
n yeast, it alters the TIM phosphorylation pattern during the late nig
ht 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 mecha
nism.