The timing, duration, and quality of sleep are regulated by an interaction between the circadian clock and homeostatic sleep pressure, which builds up during extended wakefulness. Homeostatic factors are thought to accumulate with increasing duration and intensity of wakefulness prior to sleep. In this study, a combination of behavioral monitoring and EMG/EEG recording under a pharmacological manipulation of DNA damage response markers revealed that DNA damage in neurons is a homeostatic driver for sleep. In turn, sleep increases the movements of DNA to enable efficient recruitment and activity of the DNA repair system.