Parp1 promotes sleep, which enhances DNA repair in neurons

David Zada, Yaniv Sela, Noa Matosevich, Adir Monsonego, Tali Lerer-Goldshtein, Yuval Nir, Lior Appelbaum*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)4979-4993.e7
JournalMolecular Cell
Volume81
Issue number24
DOIs
StatePublished - 16 Dec 2021

Keywords

  • DNA damage response
  • Ku80
  • NREM
  • Parp1
  • Rad52
  • chromosome dynamics
  • homeostasis
  • mice
  • sleep
  • zebrafish

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