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oai:repisalud.isciii.es:20.500.12105/176872024-11-29T23:21:56Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Murga, Matilde author Jaco, Isabel author Fan, Yuhong author Soria, Rebeca author Martinez-Pastor, Barbara author Cuadrado, Myriam author Yang, Seung-Min author Blasco, MA author Skoultchi, Arthur I author Fernandez-Capetillo, Oscar author 2007-09-24 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. J Cell Biol . 2007 ;178(7):1101-8. 10.1083/jcb.200704140 0021-9525 The Journal of cell biology 17893239 http://hdl.handle.net/20.500.12105/17687 Global chromatin compaction limits the strength of the DNA damage response.