The regulation and function of sleep are poorly understood. By studying this evolutionarily conserved behavior in a simple organism, C. elegans, we can determine basic mechanisms underlying sleep. C. elegans engages in two separately regulated sleep-like states: during lethargus (Raizen et al Nature 2008) and following exposure to stimuli that cause cellular stress such as heat shock or bacterial toxins (Hill et al Curr. Bio. 2014). Using machine vision for longitudinal tracking of quiescent behavior in individual worms, we have discovered a new stressor that induces quiescence, ultraviolet (UV) irradiation. Importantly, the quiescent response is delayed after UV exposure, suggesting that the quiescence is not a simple consequence of injury from the UV light. Additionally, UV-induced quiescence requires the ALA neuron and FLP-13 neuropeptides, similar to heat shock induced quiescence (Nelson et al Curr. Bio. 2014), indicating active neural control of the quiescent behavior. UV light induces DNA damage, which is repaired by the ATR complex; the ATR complex activates the
p53 homologue CEP-1, a transcription factor that is required for UV-induced apoptosis in the germline (Lant et al Int. J. Biol. Sci. 2010). We studied both the role of the germline and of CEP-1 signaling in the regulation of UV-induced quiescence. Animals with the
cep-1 mutant allele
gk138 show a defect in UV-induced quiescence. Preliminary results show that this defect can be rescued by transgenic expression of
cep-1, suggesting that the phenotype of the mutant is specific to the
cep-1 gene. Since
cep-1 is expressed in the germline and the pharynx (Derry et al Science 2001), we studied the role of the germline in UV-induced quiescence. We used a temperature sensitive mutant,
glp-4(
bn2), which lacks a germline when grown at the restrictive temperature. Worms that did not have a germ line showed no defect in UV-induced quiescence, suggesting that CEP-1 is signaling outside of the germline, and possibly in the pharynx. Our findings establish a novel connection between UV-induced cellular stress and regulation of sleep in C. elegans. We speculate that this connection is relevant to the well-documented phenomenon of radiation therapy induced fatigue observed in cancer patients.