Article Dans Une Revue Nucleic Acids Research Année : 2024

H2A.Z is involved in premature aging and DSB repair initiation in muscle fibers

Edwige Belotti
Nicolas Lacoste
  • Fonction : Auteur
Arslan Iftikhar
  • Fonction : Auteur
Thomas Simonet
  • Fonction : Auteur
Christophe Papin
Alexis Osseni
  • Fonction : Auteur
Nathalie Streichenberger
  • Fonction : Auteur
Pierre-Olivier Mari
  • Fonction : Auteur
Emmanuelle Girard
  • Fonction : Auteur
Mohamed Graies
  • Fonction : Auteur
Giuseppina Giglia-Mari
Stefan Dimitrov
Laurent Schaeffer

Résumé

Abstract Histone variants are key epigenetic players, but their functional and physiological roles remain poorly understood. Here, we show that depletion of the histone variant H2A.Z in mouse skeletal muscle causes oxidative stress, oxidation of proteins, accumulation of DNA damages, and both neuromuscular junction and mitochondria lesions that consequently lead to premature muscle aging and reduced life span. Investigation of the molecular mechanisms involved shows that H2A.Z is required to initiate DNA double strand break repair by recruiting Ku80 at DNA lesions. This is achieved via specific interactions of Ku80 vWA domain with H2A.Z. Taken as a whole, our data reveal that H2A.Z containing nucleosomes act as a molecular platform to bring together the proteins required to initiate and process DNA double strand break repair.

Dates et versions

hal-04784503 , version 1 (15-11-2024)

Identifiants

Citer

Edwige Belotti, Nicolas Lacoste, Arslan Iftikhar, Thomas Simonet, Christophe Papin, et al.. H2A.Z is involved in premature aging and DSB repair initiation in muscle fibers. Nucleic Acids Research, 2024, 52 (6), pp.3031-3049. ⟨10.1093/nar/gkae020⟩. ⟨hal-04784503⟩
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