Parp1 promotes sleep, which enhances DNA repair in neurons

What is your doctor's sleep protocol? Mine seemed to be, hand out sleeping pills like candy at 10pm, then have the vampire squad come in at 7am to steal blood from at least one person in the quad. Turning on the lights in the process, clinical staff efficiency, not patient wellbeing. 

Hope your doctors and hospital can get research initiated in humans.

Parp1 promotes sleep, which enhances DNA repair in neurons

 

Author links open overlay panelDavidZada¹YanivSela²NoaMatosevich²AdirMonsonego¹TaliLerer-Goldshtein¹YuvalNir²LiorAppelbaum¹³

https://doi.org/10.1016/j.molcel.2021.10.026Get rights and content

Referred to by

Ueli Schibler

PARP-1 drives slumber: A reciprocal relationship between sleep homeostasis and DNA damage repair

Molecular Cell, Volume 81, Issue 24, 16 December 2021, Pages 4958-4959

Highlights

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Neuronal DNA damage triggers sleep

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Sleep increases DNA repair and reduces cellular homeostatic pressure

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Activity of the DNA damage detector Parp1 increases with sleep deprivation

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Parp1 activity promotes sleep, chromosome dynamics, and DNA repair

Summary

The characteristics of the sleep drivers and the mechanisms through which sleep relieves the cellular homeostatic pressure are unclear. In flies, zebrafish, mice, and humans, DNA damage levels increase during wakefulness and decrease during sleep. Here, we show that 6 h of consolidated sleep is sufficient to reduce DNA damage in the zebrafish dorsal pallium. Induction of DNA damage by neuronal activity and mutagens triggered sleep and DNA repair. The activity of the DNA damage response (DDR) proteins Rad52 and Ku80 increased during sleep, and chromosome dynamics enhanced Rad52 activity. The activity of the DDR initiator poly(ADP-ribose) polymerase 1 (Parp1) increased following sleep deprivation. In both larva zebrafish and adult mice, Parp1 promoted sleep. Inhibition of Parp1 activity reduced sleep-dependent chromosome dynamics and repair. These results demonstrate that DNA damage is a homeostatic driver for sleep, and Parp1 pathways can sense this cellular pressure and facilitate sleep and repair activity.

Graphical abstract

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