Abstract
The period protein (PER) is a well-studied repressor of clock gene transcription in Drosophila. Two of the original three mutants, period-Short (per S) and period-Long (perL ), dramatically alter the rhythms of flies. However, the mechanisms that underlie these missense mutations and how they affect PER function are not well-understood. In this work, we show that the degradation of PERS is significantly faster than PER both in cell culture and in flies. Because PER as well as PERS is stabilized by protein TIMELESS (TIM), this difference only occurs after TIM degradation. The different degradation rates of PER and PERS underlie the different responses to light of wild-type and per S flies. We also found that the arrhythmic phenotype caused by the loss of neuropeptide PDF in pdf-null animals can be rescued by the perS mutant. By studying this phenomenon, a connection between PDF and PER stability via the activation of PKA was discovered. Although the data about the perL mutation presented in this thesis are still descriptive rather than conclusive, it is quite clear that this mutation causes a series of changes in the transcription of clock genes as well as the CLK-PER and CLK-DNA interactions, the modification of CLK and the binding partners of CLK.