Global chromatin compaction limits the strength of the DNA damage response

Matilde Murga, Isabel Jaco, Yuhong Fan, Rebeca Soria, Barbara Martinez-Pastor, Myriam Cuadrado, Seung Min Yang, Maria A. Blasco, Arthur I. Skoultchi, Oscar Fernandez-Capetillo

Research output: Contribution to journalArticle

171 Scopus citations

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 configuration might account for the cell-to-cell variation in the strength of the DDR observed when groups of cells are challenged with DNA breaks.

Original languageEnglish (US)
Pages (from-to)1101-1108
Number of pages8
JournalJournal of Cell Biology
Volume178
Issue number7
DOIs
StatePublished - Sep 24 2007

ASJC Scopus subject areas

  • Cell Biology

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