%0 Journal Article %1 Szilard2010Systematic %A Szilard, Rachel K. %A Jacques, Pierre-Etienne %A Laramee, Louise %A Cheng, Benjamin %A Galicia, Sarah %A Bataille, Alain R. %A Yeung, ManTek %A Mendez, Megan %A Bergeron, Maxime %A Robert, Francois %A Durocher, Daniel %D 2010 %I Nature Publishing Group %J Nature Structural & Molecular Biology %K genetics yeast %N 3 %P 299--305 %R 10.1038/nsmb.1754 %T Systematic identification of fragile sites via genome-wide location analysis of gamma-H2AX %U http://dx.doi.org/10.1038/nsmb.1754 %V 17 %X 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 γ-H2A (yeast γ-H2AX) in a Mec1 (ATR)- and Tel1 (ATM)-dependent manner. Here, we describe the genome-wide location analysis of γ-H2A as a strategy to identify loci prone to engaging the Mec1 and Tel1 pathways. Notably, γ-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 γ-H2A map to repressed protein-coding genes, and histone deacetylases are necessary for formation of γ-H2A at these loci. Finally, our work indicates that high-resolution mapping of γ-H2AX is a fruitful route to map fragile sites in eukaryotic genomes.

@article{Szilard2010Systematic, 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 {γ-H2A} (yeast {γ-H2AX}) in a Mec1 ({ATR})- and Tel1 ({ATM})-dependent manner. Here, we describe the genome-wide location analysis of {γ-H2A} as a strategy to identify loci prone to engaging the Mec1 and Tel1 pathways. Notably, {γ-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 {γ-H2A} map to repressed protein-coding genes, and histone deacetylases are necessary for formation of {γ-H2A} at these loci. Finally, our work indicates that high-resolution mapping of {γ-H2AX} is a fruitful route to map fragile sites in eukaryotic genomes.}, added-at = {2018-12-02T16:09:07.000+0100}, author = {Szilard, Rachel K. and Jacques, Pierre-Etienne and Laramee, Louise and Cheng, Benjamin and Galicia, Sarah and Bataille, Alain R. and Yeung, ManTek and Mendez, Megan and Bergeron, Maxime and Robert, Francois and Durocher, Daniel}, biburl = {https://www.bibsonomy.org/bibtex/2c39ac11c8c6ee86206f6eeba537775c6/karthikraman}, citeulike-article-id = {6661760}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nsmb.1754}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nsmb.1754}, day = 07, doi = {10.1038/nsmb.1754}, interhash = {8376051ba663dfa81a257d1ac339929d}, intrahash = {c39ac11c8c6ee86206f6eeba537775c6}, issn = {1545-9993}, journal = {Nature Structural \& Molecular Biology}, keywords = {genetics yeast}, month = mar, number = 3, pages = {299--305}, posted-at = {2010-02-14 07:52:22}, priority = {2}, publisher = {Nature Publishing Group}, timestamp = {2018-12-02T16:09:07.000+0100}, title = {Systematic identification of fragile sites via genome-wide location analysis of [{gamma]-H2AX}}, url = {http://dx.doi.org/10.1038/nsmb.1754}, volume = 17, year = 2010 }