Previous behavioral
screens to find genes involved in Drosophila circadian
rhythms have identified two major players: period
(1) and timeless (2). We are conducting EMS mutagenesis/behavioral
screens to identify other clock genes. Our strategy is
to find either suppressors or enhancers of perL,
on the assumption that it might be easier to uncover important
clock components starting from a mutant rather than from
a wild-type clock. We have identified a number of candidate
mutants, which are in various stages of analysis.
Currently we
are characterizing a mutant named cycle which has
a semi-dominant phenotype. Flies that are homozygous for
the cyc0 mutation are arrhythmic, while heterozygotes
have periods that are 1 hour longer than wild-type. Unlike
the timSL mutant, a previous mutant obtained from
this screen (3), this mutation is insensitive to the per
genotype. An interesting feature of these flies is that
they make very low, non-cycling levels not only of PER
and TIM protein, but of per and tim mRNA
as well. The defect appears to be transcriptional, since
mutant flies fail to turn on per and tim
transcription as shown by nuclear run-on experiments.
We are now in the process of cloning this new mutation
to determine if, in fact, it codes for a circadian-specific
transcription factor.
