Global chromatin mobility induced by a DSB is dictated by chromosomal conformation and defines the HR outcome.

S. cerevisiae chromatin dynamics chromosome organization chromosomes double-strand break gene expression genetics genomics homologous recombination yeast γ-H2A(X)

Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
20 09 2022
Historique:
received: 19 02 2022
accepted: 08 09 2022
entrez: 20 9 2022
pubmed: 21 9 2022
medline: 24 9 2022
Statut: epublish

Résumé

Repair of DNA double-strand breaks (DSBs) is crucial for genome integrity. A conserved response to DSBs is an increase in chromatin mobility that can be local, at the site of the DSB, or global, at undamaged regions of the genome. Here, we address the function of global chromatin mobility during homologous recombination (HR) of a single, targeted, controlled DSB. We set up a system that tracks HR in vivo over time and show that two types of DSB-induced global chromatin mobility are involved in HR, depending on the position of the DSB. Close to the centromere, a DSB induces global mobility that depends solely on H2A(X) phosphorylation and accelerates repair kinetics, but is not essential. In contrast, the global mobility induced by a DSB away from the centromere becomes essential for HR repair and is triggered by homology search through a mechanism that depends on H2A(X) phosphorylation, checkpoint progression, and Rad51. Our data demonstrate that global mobility is governed by chromosomal conformation and differentially coordinates repair by HR.

Identifiants

pubmed: 36125964
doi: 10.7554/eLife.78015
pii: 78015
pmc: PMC9489209
doi:
pii:

Substances chimiques

Chromatin 0
DNA 9007-49-2

Banques de données

Dryad
['10.5061/dryad.931zcrjn1']

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2022, García Fernández, Almayrac et al.

Déclaration de conflit d'intérêts

FG, EA, ÀC, RB, YK, MB, EF No competing interests declared

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Auteurs

Fabiola García Fernández (F)

Université de Paris, IRSL, INSERM, U944, CNRS, UMR7212, Paris, France.

Etienne Almayrac (E)

Université de Paris, IRSL, INSERM, U944, CNRS, UMR7212, Paris, France.

Ànnia Carré Simon (À)

Université de Paris, IRSL, INSERM, U944, CNRS, UMR7212, Paris, France.

Renaud Batrin (R)

Université de Paris, IRSL, INSERM, U944, CNRS, UMR7212, Paris, France.

Yasmine Khalil (Y)

Université de Paris, IRSL, INSERM, U944, CNRS, UMR7212, Paris, France.

Michel Boissac (M)

Université de Paris, IRSL, INSERM, U944, CNRS, UMR7212, Paris, France.

Emmanuelle Fabre (E)

Université de Paris, IRSL, INSERM, U944, CNRS, UMR7212, Paris, France.

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Classifications MeSH