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Mol Cell. 2011 Mar 4;41(5):529-42. doi: 10.1016/j.molcel.2011.02.015.

Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks.

Author information

1
The David and Inez Myers Laboratory for Genetic Research, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

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.

PMID:
21362549
PMCID:
PMC3397146
DOI:
10.1016/j.molcel.2011.02.015
[Indexed for MEDLINE]
Free PMC Article
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