Neuronal Progenitors Suffer Genotoxic Stress in the Clock Mutant .

The physiological role and the molecular architecture of the circadian clock in fully developed organisms are well established. Yet, we have a limited understanding of the function of the clock during ontogenesis. We have used a null mutant () of the clock gene () in to ask whether PER may play a role during normal brain development. In third-instar larvae, we have observed that the absence of functional results in increased genotoxic stress compared to wild-type controls. We have detected increased double-strand DNA breaks in the central nervous system and chromosome aberrations in dividing neuronal precursor cells. We have demonstrated that reactive oxygen species (ROS) are causal to the genotoxic effect and that expression of PER in glia is necessary and sufficient to suppress such a phenotype. Finally, we have shown that the absence of PER may result in less condensed chromatin, which contributes to DNA damage.