SUPPRESSION OF PERIOD PROTEIN ABUNDANCE AND CIRCADIAN CYCLING BY THE DROSOPHILA CLOCK MUTATION TIMELESS

The timeless mutation (tim) leads to loss of circadian behavioral rhyt hms in Drosophila melanogaster. The effects of tim on rhythmicity invo lve interactions with period (per), a second essential clock gene, as the tim mutation suppresses circadian oscillations of per transcriptio n and blocks nuclear localization of a PER reporter protein, In the pr esent study it was found that the tim mutant constitutively produces a low level of PER protein that is comparable with that produced late i n the day by wild-type flies. In addition, it was shown that tim suppr esses circadian cycling of PER protein abundance and circadian regulat ion of PER phosphorylation. Transfer of wild-type flies to constant li ght also suppressed cycling of PER abundance and phosphorylation and p roduced constitutively low levels of PER, In the tim mutant there was no additional effect of constant light on PER, These results suggest t hat constant light and the tim mutation produce related changes in the underlying biological clock, We further suggest that the multiple eff ects of tim are due to a primary effect on per expression at the postt ranscriptional level, The effects of tim on behavioral rhythms and per RNA cycling are therefore likely to involve effects on PER protein th rough previously proposed feedback mechanisms.