Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks.
Mol Cell
; 41(5): 529-42, 2011 Mar 04.
Article
em En
| MEDLINE
| ID: mdl-21362549
ABSTRACT
The cellular response to DNA double-strand breaks (DSBs) is mobilized by the protein kinase ATM, which phosphorylates key players in the DNA damage response (DDR) network. A major question is how ATM controls DSB repair. Optimal repair requires chromatin relaxation at damaged sites. Chromatin reorganization is coupled to dynamic alterations in histone posttranslational modifications. Here, we show that in human cells, DSBs induce monoubiquitylation of histone H2B, a modification that is associated in undamaged cells with transcription elongation. We find that this process relies on recruitment to DSB sites and ATM-dependent phosphorylation of the responsible E3 ubiquitin ligase the RNF20-RNF40 heterodimer. H2B monoubiquitylation is required for timely recruitment of players in the two major DSB repair pathways-nonhomologous end-joining and homologous recombination repair-and optimal repair via both pathways. Our data and previous data suggest a two-stage model for chromatin decondensation that facilitates DSB repair.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Histonas
/
Proteínas Serina-Treonina Quinases
/
Proteínas de Ciclo Celular
/
Proteínas Supressoras de Tumor
/
Ubiquitina
/
Proteínas de Ligação a DNA
/
Reparo do DNA
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article