Nuclear ARP2/3 drives DNA break clustering for homology-directed repair.
Nature
; 559(7712): 61-66, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29925947
ABSTRACT
DNA double-strand breaks repaired by non-homologous end joining display limited DNA end-processing and chromosomal mobility. By contrast, double-strand breaks undergoing homology-directed repair exhibit extensive processing and enhanced motion. The molecular basis of this movement is unknown. Here, using Xenopus laevis cell-free extracts and mammalian cells, we establish that nuclear actin, WASP, and the actin-nucleating ARP2/3 complex are recruited to damaged chromatin undergoing homology-directed repair. We demonstrate that nuclear actin polymerization is required for the migration of a subset of double-strand breaks into discrete sub-nuclear clusters. Actin-driven movements specifically affect double-strand breaks repaired by homology-directed repair in G2 cell cycle phase; inhibition of actin nucleation impairs DNA end-processing and homology-directed repair. By contrast, ARP2/3 is not enriched at double-strand breaks repaired by non-homologous end joining and does not regulate non-homologous end joining. Our findings establish that nuclear actin-based mobility shapes chromatin organization by generating repair domains that are essential for homology-directed repair in eukaryotic cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Xenopus laevis
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Núcleo Celular
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Complexo 2-3 de Proteínas Relacionadas à Actina
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Quebras de DNA de Cadeia Dupla
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Reparo de DNA por Recombinação
Limite:
Animals
Idioma:
En
Revista:
Nature
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos