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


Journal

Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374

Informations de publication

Date de publication:
05 2023
Historique:
received: 27 08 2021
accepted: 28 03 2023
medline: 19 5 2023
pubmed: 28 4 2023
entrez: 27 4 2023
Statut: ppublish

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.

Identifiants

pubmed: 37106138
doi: 10.1038/s41594-023-00977-x
pii: 10.1038/s41594-023-00977-x
doi:

Substances chimiques

Histones 0
Chromatin 0
Poly(ADP-ribose) Polymerases EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1 EC 2.4.2.30
DNA 9007-49-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

678-691

Subventions

Organisme : Wellcome Trust
ID : 210634
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 223107
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R007195/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C35050/A22284
Pays : United Kingdom

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Rebecca Smith (R)

University of Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes) - UMR 6290, BIOSIT - UMS3480, Rennes, France. rebecca.smith@path.ox.ac.uk.
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. rebecca.smith@path.ox.ac.uk.

Siham Zentout (S)

University of Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes) - UMR 6290, BIOSIT - UMS3480, Rennes, France.

Magdalena Rother (M)

Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.

Nicolas Bigot (N)

University of Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes) - UMR 6290, BIOSIT - UMS3480, Rennes, France.

Catherine Chapuis (C)

University of Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes) - UMR 6290, BIOSIT - UMS3480, Rennes, France.

Alexandra Mihuț (A)

Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, Biological Research Centre, Eötvös Loránd Research Network (ELKH), Szeged, Hungary.
Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Szeged, Hungary.

Florian Franz Zobel (FF)

Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

Ivan Ahel (I)

Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

Haico van Attikum (H)

Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.

Gyula Timinszky (G)

Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, Biological Research Centre, Eötvös Loránd Research Network (ELKH), Szeged, Hungary. timinszky.gyula@brc.hu.

Sébastien Huet (S)

University of Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes) - UMR 6290, BIOSIT - UMS3480, Rennes, France. sebastien.huet@univ-rennes.fr.
Institut Universitaire de France, Paris, France. sebastien.huet@univ-rennes.fr.

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