Global chromatin compaction limits the strength of the DNA damage response

Content Provider	Scilit
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
Copyright Year	2007
Description	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.
Related Links	http://jcb.rupress.org/content/jcb/178/7/1101.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064646/pdf
Ending Page	1108
Page Count	8
Starting Page	1101
DOI	10.1083/jcb.200704140
Journal	Journal of Cell Biology
Issue Number	7
Volume Number	178
Language	English
Publisher	Rockefeller University Press
Publisher Date	2007-09-24
Access Restriction	Open
Subject Keyword	Biochemistry and Molecular Biology Dna Damage Telomere Chromatin Embryonic Stem Cells Histones Journal: Journal of Cell Biology (Vol- 178, Issue- 7)
Content Type	Text