HPF1-dependent histone ADP-ribosylation triggers chromatin relaxation to promote the recruitment of repair factors at sites of DNA damage - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Nature Structural and Molecular Biology Année : 2023

HPF1-dependent histone ADP-ribosylation triggers chromatin relaxation to promote the recruitment of repair factors at sites of DNA damage

Résumé

Poly(ADP-ribose) polymerase 1 (PARP1) activity is regulated by its co-factor histone poly(ADP-ribosylation) factor 1 (HPF1). The complex formed by HPF1 and PARP1 catalyzes ADP-ribosylation of serine residues of proteins near DNA breaks, mainly PARP1 and histones. However, the effect of HPF1 on DNA repair regulated by PARP1 remains unclear. Here, we show that HPF1 controls prolonged histone ADP-ribosylation in the vicinity of the DNA breaks by regulating both the number and length of ADP-ribose chains. Furthermore, we demonstrate that HPF1-dependent histone ADP-ribosylation triggers the rapid unfolding of chromatin, facilitating access to DNA at sites of damage. This process promotes the assembly of both the homologous recombination and non-homologous end joining repair machineries. Altogether, our data highlight the key roles played by the PARP1/HPF1 complex in regulating ADP-ribosylation signaling as well as the conformation of damaged chromatin at early stages of the DNA damage response.

Domaines

Génétique

Dates et versions

hal-04089195 , version 1 (04-05-2023)

Identifiants

Citer

Rebecca Smith, Siham Zentout, Magdalena Rother, Nicolas Bigot, Catherine Chapuis, et al.. HPF1-dependent histone ADP-ribosylation triggers chromatin relaxation to promote the recruitment of repair factors at sites of DNA damage. Nature Structural and Molecular Biology, 2023, 30 (5), pp.678-691. ⟨10.1038/s41594-023-00977-x⟩. ⟨hal-04089195⟩
21 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More