Parp1 promotes sleep, which enhances DNA repair in neurons.


Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
16 12 2021
Historique:
received: 24 02 2021
revised: 18 10 2021
accepted: 26 10 2021
pubmed: 20 11 2021
medline: 15 2 2022
entrez: 19 11 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34798058
pii: S1097-2765(21)00933-3
doi: 10.1016/j.molcel.2021.10.026
pmc: PMC8688325
mid: NIHMS1754751
pii:
doi:

Substances chimiques

DNA-Binding Proteins 0
Ku Autoantigen EC 4.2.99.-
Parp1 protein, mouse EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1 EC 2.4.2.30
Rad52 DNA Repair and Recombination Protein 0
Rad52 protein, mouse 0
Rad52 protein, zebrafish 0
Xrcc5 protein, mouse EC 3.6.4.12
Zebrafish Proteins 0
Parp1 protein, zebrafish 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

4979-4993.e7

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH116470
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

David Zada (D)

The Faculty of Life Sciences and the Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 5290002, Israel.

Yaniv Sela (Y)

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo 69978, Israel.

Noa Matosevich (N)

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo 69978, Israel.

Adir Monsonego (A)

The Faculty of Life Sciences and the Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 5290002, Israel.

Tali Lerer-Goldshtein (T)

The Faculty of Life Sciences and the Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 5290002, Israel.

Yuval Nir (Y)

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo 69978, Israel.

Lior Appelbaum (L)

The Faculty of Life Sciences and the Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 5290002, Israel. Electronic address: lior.appelbaum@biu.ac.il.

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Classifications MeSH