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.
%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
}