@article{e2d1585674a24203a461560afc7aa60d,
title = "Requirement of ATM-Dependent Monoubiquitylation of Histone H2B for Timely Repair of DNA Double-Strand Breaks",
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.",
author = "Lilach Moyal and Yaniv Lerenthal and Mali Gana-Weisz and Gilad Mass and Sairei So and Wang, {Shih Ya} and Berina Eppink and Chung, {Young Min} and Gil Shalev and Efrat Shema and Dganit Shkedy and Smorodinsky, {Nechama I.} and {van Vliet}, Nicole and Bernhard Kuster and Matthias Mann and Aaron Ciechanover and Jochen Dahm-Daphi and Roland Kanaar and Hu, {Mickey C.T.} and Chen, {David J.} and Moshe Oren and Yosef Shiloh",
note = "Funding Information: We thank Ruth Shiloh for critical advice, Yaron Pereg and Rami Khosravi for experimental contributions and advice, Yael Ziv for useful discussions and comments on the manuscript, J. Lukas for cell lines stably expressing GFP-tagged RNF8 and MDC1, M. Lavin for the C3ABR cell line, M. Huen for anti-RNF8 antibody, N. Mailand for the anti-RNF8 antibody and siRNA, M. Goldberg for anti-MDC1 antibody and siRNA, and T. Halazonetis for the α-53BP1 antibody. This work was supported by research grants from The Israel Science Foundation, the A-T Medical Research Foundation, The A-T Children's Project and the Israel Cancer Research Fund (to Y.S.), a core grant from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to Y.S., A.C., and M.O.), grants from The National Institutes of Health (CA50519 and PO1-CA92584, to D.J.C), the National Cancer Institute (R01 CA113859 to M.C.-T.H. and R37 CA40099 to M.O.), the Netherlands Genomic Initiative/Netherlands Organization for Scientific Research (NWO), Chemical Sciences TOP, and the Dutch Cancer Society (KWF) (to R.K.), and a grant from the German Federal Ministry of Education and Research (BMBF 02S8427) to J.D.-D. Y.S. is a Research Professor of the Israel Cancer Research Fund. ",
year = "2011",
month = mar,
day = "4",
doi = "10.1016/j.molcel.2011.02.015",
language = "אנגלית",
volume = "41",
pages = "529--542",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",
}