Requirement of ATM-Dependent Monoubiquitylation of Histone H2B for Timely Repair of DNA Double-Strand Breaks

Lilach Moyal, Yaniv Lerenthal, Mali Gana-Weisz, Gilad Mass, Sairei So, Shih Ya Wang, Berina Eppink, Young Min Chung, Gil Shalev, Efrat Shema, Dganit Shkedy, Nechama I. Smorodinsky, Nicole van Vliet, Bernhard Kuster, Matthias Mann, Aaron Ciechanover, Jochen Dahm-Daphi, Roland Kanaar, Mickey C T Hu, David J. ChenMoshe Oren, Yosef Shiloh

Research output: Contribution to journalArticle

221 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)529-542
Number of pages14
JournalMolecular cell
Volume41
Issue number5
DOIs
StatePublished - Mar 4 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Moyal, L., Lerenthal, Y., Gana-Weisz, M., Mass, G., So, S., Wang, S. Y., Eppink, B., Chung, Y. M., Shalev, G., Shema, E., Shkedy, D., Smorodinsky, N. I., van Vliet, N., Kuster, B., Mann, M., Ciechanover, A., Dahm-Daphi, J., Kanaar, R., Hu, M. C. T., ... Shiloh, Y. (2011). Requirement of ATM-Dependent Monoubiquitylation of Histone H2B for Timely Repair of DNA Double-Strand Breaks. Molecular cell, 41(5), 529-542. https://doi.org/10.1016/j.molcel.2011.02.015