Rest and Repair: How dPARP and DNA Damage Influence Sleep

What are the evolutionary advantages of sleep? Although it is well established that sleep is a highly conserved behavior throughout the animal kingdom, its precise biological purpose is still unclear. Several theories have been put forward to explain its role. For instance, sleep has been linked to processes such as memory consolidation, synaptic remodeling, and the clearance of neurotoxic by-products that accumulate in the extracellular space during periods of wakefulness. More recently, a novel hypothesis has emerged suggesting that the repair of DNA damage accumulated while awake constitutes a core function of sleep in zebrafish. Could this mechanism be conserved across other animals? Might DNA repair proteins serve as critical molecular sensors in the regulation of sleep? We propose that DNA repair proteins contribute to the molecular machinery of the sleep homeostat in Drosophila. We are evaluating whether dPARP, a protein identified as a key detector of DNA double-strand breaks and mediator of sleep induction in fish, also fulfills this role in insects.