Journal
MOLECULAR CELL
Volume 41, Issue 5, Pages 529-542Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2011.02.015
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Funding
- Israel Science Foundation
- A-T Medical Research Foundation
- A-T Children's Project
- Israel Cancer Research Fund
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- National Institutes of Health [CA50519, PO1-CA92584]
- National Cancer Institute [R01 CA113859, R37 CA40099]
- Netherlands Genomic Initiative/Netherlands Organization for Scientific Research (NWO)
- Chemical Sciences TOP
- Dutch Cancer Society
- German Federal Ministry of Education and Research [BMBF 02S8427]
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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.
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