Neuronal progenitors suffer genotoxic stress in theDrosophilaclock mutantper0

Abstract

AbstractThe physiological role and the molecular architecture of the circadian clock in fully developed organisms are well established. Yet, we have a limited understanding about the function of the clock during ontogenesis. We have used a null mutant (per0) of the clock geneperiod(per) inDrosophila melanogasterto ask whether PER may play a role during normal brain development. In 3rdinstar larvae, we have observed that absence of functionalperresults 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, preliminary evidence indicates that absence of PER may result in less condensed chromatin, which may contribute to DNA damage.