Contribution of sleep to the repair of neuronal DNA double-strand breaks: evidence from flies and mice.
Exploration of a novel environment leads to neuronal DNA double-strand breaks (DSBs). These DSBs are generated by type 2 topoisomerase to relieve topological constrains that limit transcription of plasticity-related immediate early genes. If not promptly repaired, however, DSBs may lead to cell death. Since the induction of plasticity-related genes is higher in wake than in sleep, we asked whether it is specifically wake associated with synaptic plasticity that leads to DSBs, and whether sleep provides any selective advantage over wake in their repair. In flies and mice, we find that enriched wake, more than simply time spent awake, induces DSBs, and their repair in mice is delayed or prevented by subsequent wake. In both species the repair of irradiation-induced neuronal DSBs is also quicker during sleep, and mouse genes mediating the response to DNA damage are upregulated in sleep. Thus, sleep facilitates the repair of neuronal DSBs.
Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Blvd, Madison, WI 53719, USA.|Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche, Ancona, Italy.
Michele
M
Bellesi
Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Blvd, Madison, WI 53719, USA.
Daniel
D
Bushey
Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Blvd, Madison, WI 53719, USA.
Mattia
M
Chini
Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Blvd, Madison, WI 53719, USA.
Giulio
G
Tononi
Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Blvd, Madison, WI 53719, USA.
Chiara
C
Cirelli
D000818:Animals; D001921:Brain / Q000473:pathology / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology* / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000235:genetics; D012890:Sleep; D015533:Transcriptional Activation
D045643:DNA Repair Enzymes