Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
02 Feb 2024
Historique:
received: 09 03 2023
accepted: 16 01 2024
medline: 3 2 2024
pubmed: 3 2 2024
entrez: 2 2 2024
Statut: epublish

Résumé

The chromatin remodeler ALC1 is activated by DNA damage-induced poly(ADP-ribose) deposited by PARP1/PARP2 and their co-factor HPF1. ALC1 has emerged as a cancer drug target, but how it is recruited to ADP-ribosylated nucleosomes to affect their positioning near DNA breaks is unknown. Here we find that PARP1/HPF1 preferentially initiates ADP-ribosylation on the histone H2B tail closest to the DNA break. To dissect the consequences of such asymmetry, we generate nucleosomes with a defined ADP-ribosylated H2B tail on one side only. The cryo-electron microscopy structure of ALC1 bound to such an asymmetric nucleosome indicates preferential engagement on one side. Using single-molecule FRET, we demonstrate that this asymmetric recruitment gives rise to directed sliding away from the DNA linker closest to the ADP-ribosylation site. Our data suggest a mechanism by which ALC1 slides nucleosomes away from a DNA break to render it more accessible to repair factors.

Identifiants

pubmed: 38307862
doi: 10.1038/s41467-024-45237-8
pii: 10.1038/s41467-024-45237-8
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1000

Subventions

Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : ERC Starting Grant 714068
Organisme : Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)
ID : KAW 019.0306
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2019-03534
Organisme : Cancerfonden (Swedish Cancer Society)
ID : 19 0055 Pj

Informations de copyright

© 2024. The Author(s).

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Auteurs

Luka Bacic (L)

Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75124, Uppsala, Sweden.

Guillaume Gaullier (G)

Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75124, Uppsala, Sweden.
Department of Chemistry - Ångström, Uppsala University, 75120, Uppsala, Sweden.

Jugal Mohapatra (J)

Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.

Guanzhong Mao (G)

Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75124, Uppsala, Sweden.

Klaus Brackmann (K)

Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75124, Uppsala, Sweden.

Mikhail Panfilov (M)

Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75124, Uppsala, Sweden.

Glen Liszczak (G)

Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.

Anton Sabantsev (A)

Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75124, Uppsala, Sweden. anton.sabantcev@icm.uu.se.

Sebastian Deindl (S)

Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75124, Uppsala, Sweden. sebastian.deindl@icm.uu.se.

Classifications MeSH