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- Title
Systematic identification of fragile sites via genome-wide location analysis of gamma-H2AX.
- Authors
Szilard, Rachel K; Jacques, Pierre-Etienne; Laramée, Louise; Cheng, Benjamin; Galicia, Sarah; Bataille, Alain R; Yeung, ManTek; Mendez, Megan; Bergeron, Maxime; Robert, François; Durocher, Daniel
- Abstract
Phosphorylation of histone H2AX is an early response to DNA damage in eukaryotes. In Saccharomyces cerevisiae, DNA damage or replication-fork stalling results in phosphorylation of histone H2A yielding gamma-H2A (yeast gamma-H2AX) in a Mec1 (ATR)- and Tel1 (ATM)-dependent manner. Here, we describe the genome-wide location analysis of gamma-H2A as a strategy to identify loci prone to engaging the Mec1 and Tel1 pathways. Notably, gamma-H2A enrichment overlaps with loci prone to replication-fork stalling and is caused by the action of Mec1 and Tel1, indicating that these loci are prone to breakage. Moreover, about half the sites enriched for gamma-H2A map to repressed protein-coding genes, and histone deacetylases are necessary for formation of gamma-H2A at these loci. Finally, our work indicates that high-resolution mapping of gamma-H2AX is a fruitful route to map fragile sites in eukaryotic genomes.
- Publication
Nature structural & molecular biology, 2010, Vol 17, Issue 3, p299
- ISSN
1545-9985
- Publication type
Journal Article
- DOI
10.1038/nsmb.1754