Journal
MOLECULAR CELL
Volume 52, Issue 4, Pages 583-590Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2013.10.006
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Funding
- Spanish Ministry of Economy and Competitiveness [Consolider Ingenio 2010 CSD2007-0015, BFU2010-16372]
- Junta de Andalucia [CVI-4567]
- European Union (FEDER)
- Spanish National Institute of Health Carlos III
- Consejo Superior de Investigaciones Cientificas (CSIC)
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R loops are transcription byproducts that constitute a threat to genome integrity. Here we show that R loops are tightly linked to histone H3 S10 phosphorylation (H3S10P), a mark of chromatin condensation. Chromatin immunoprecipitation (ChIP)-on-chip (ChIP-chip) analyses reveal H3S10P accumulation at centromeres, pericentromeric chromatin, and a large number of active open reading frames (ORFs) in R-loop-accumulating yeast cells, better observed in G1. Histone H3S10 plays a key role in maintaining genome stability, as scored by ectopic recombination and plasmid loss, Rad52 foci, and Rad53 checkpoint activation. H3S10P coincides with the presence of DNA-RNA hybrids, is suppressed by ribonuclease H overexpression, and causes reduced accessibility of restriction endonucleases, implying a tight connection between R loops, H3S10P, and chromatin compaction. Such histone modifications were also observed in R-loop-accumulating Caenorhabditis elegans and He La cells. We therefore provide a role of RNA in chromatin structure essential to understand how R loops modulate genome dynamics.
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