PUBLICATION
Parp1 promotes sleep, which enhances DNA repair in neurons
- Authors
- Zada, D., Sela, Y., Matosevich, N., Monsonego, A., Lerer-Goldshtein, T., Nir, Y., Appelbaum, L.
- ID
- ZDB-PUB-211120-7
- Date
- 2021
- Source
- Molecular Cell 81(24): 4979-4993.e7 (Journal)
- Registered Authors
- Appelbaum, Lior, Zada, David
- Keywords
- DNA damage response, Ku80, NREM, Parp1, Rad52, chromosome dynamics, homeostasis, mice, sleep, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Behavior, Animal*
- Brain/enzymology*
- Brain/pathology
- Brain/physiopathology
- DNA Damage*
- DNA Repair*
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Female
- Ku Autoantigen/genetics
- Ku Autoantigen/metabolism
- Male
- Mice, Inbred C57BL
- Neurons/enzymology*
- Neurons/pathology
- Poly (ADP-Ribose) Polymerase-1/genetics
- Poly (ADP-Ribose) Polymerase-1/metabolism*
- Rad52 DNA Repair and Recombination Protein/genetics
- Rad52 DNA Repair and Recombination Protein/metabolism
- Sleep*
- Time Factors
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 34798058 Full text @ Mol. Cell
Citation
Zada, D., Sela, Y., Matosevich, N., Monsonego, A., Lerer-Goldshtein, T., Nir, Y., Appelbaum, L. (2021) Parp1 promotes sleep, which enhances DNA repair in neurons. Molecular Cell. 81(24):4979-4993.e7.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping