Sleep loss lowers the cold-inducible DNA-repair factor CIRBP in the mouse brain: a cross-dataset re-analysis supporting a temperature-gated model of sleep-dependent DNA repair

Sleep helps neurons repair DNA double-strand breaks, but what links sleep to repair is unclear. Two separate findings point to one candidate. The cold-inducible RNA-binding protein CIRBP promotes double-strand-break repair and underlies enhanced repair in the long-lived bowhead whale. Its expression in the brain also falls when waking warms the cortex. We propose that sleep-dependent DNA repair is partly temperature-gated through CIRBP, which PARP1 recruits to DNA breaks. We tested the first link of this model by re-analysing three public mouse brain transcriptome datasets of acute sleep deprivation (two hippocampal, one frontal cortex; 3 laboratories; 45 animals). Cirbp was reduced after sleep loss in every dataset (log2 fold change -0.51 to -1.06; each p < 10^-4). Random-effects pooling gave a Hedges' g of -4.85 (95% CI -7.36 to -2.33; p = 1.6 x 10^-4). The related cold-inducible gene Rbm3 was not consistently changed. Cirbp did not co-vary with DNA-repair gene expression within groups. In human whole blood after a week of restricted sleep, CIRBP was unchanged. The brain-specific Cirbp response fits a temperature-gated repair model, but transcript data cannot show that CIRBP drives repair. We set out three falsifiable experiments, including neuronal gamma-H2AX measurement in Cirbp-knockout mice.