Global chromatin compaction limits the strength of the DNA damage response

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Title: Global chromatin compaction limits the strength of the DNA damage response
Author: Murga, Matilde ; Jaco, Isabel ; Fan, Yuhong ; Soria, Rebeca ; Martinez-Pastor, Barbara ; Cuadrado, Myriam ; Yang, Seung-Min ; Blasco, Maria A. ; Skoultchi, Arthur I. ; Fernandez-Capetillo, Oscar
Abstract: In response to DNA damage, chromatin undergoes a global decondensation process that has been proposed to facilitate genome surveillance. However, the impact that chromatin compaction has on the DNA damage response (DDR) has not directly been tested and thus remains speculative. We apply two independent approaches (one based on murine embryonic stem cells with reduced amounts of the linker histone H1 and the second making use of histone deacetylase inhibitors) to show that the strength of the DDR is amplified in the context of “open” chromatin. H1-depleted cells are hyperresistant to DNA damage and present hypersensitive checkpoints, phenotypes that we show are explained by an increase in the amount of signaling generated at each DNA break. Furthermore, the decrease in H1 leads to a general increase in telomere length, an as of yet unrecognized role for H1 in the regulation of chromosome structure. We propose that slight differences in the epigenetic confi guration might account for the cell-to-cell variation in the strength of the DDR observed when groups of cells are challenged with DNA breaks.
Description: ©2007 Murga et al. DOI: 10.1083/jcb.200704140
Type: Article
ISSN: 0021-9525
Citation: Matilde Murga, Isabel Jaco, Yuhong Fan, Rebeca Soria, Barbara Martinez-Pastor, Myriam Cuadrado, Seung-Min Yang, Maria A. Blasco, Arthur I. Skoultchi, and Oscar Fernandez-Capetillo, “Global chromatin compaction limits the strength of the DNA damage response,” Journal of Cell Biology, (2007) Vol. 178, No. 7, 1101-1108.
Date: 2007-09-24
Contributor: Spanish National Cancer Center. Molecular Oncology Programme
Albert Einstein College of Medicine. Dept. of Cell Biology
Publisher: Georgia Institute of Technology
Rockefeller University Press
Subject: DNA damage response
Chromatin compaction
Telomere length

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