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Reference: Szilard RK, et al. (2010) Systematic identification of fragile sites via genome-wide location analysis of gamma-H2AX. Nat Struct Mol Biol 17(3):299-305

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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.

Reference Type
Journal Article
Authors
Szilard RK, Jacques PE, Laramee L, Cheng B, Galicia S, Bataille AR, Yeung M, Mendez M, Bergeron M, Robert F, ... Show all
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