Double-strand break (DSB) damage in yeast and mammalian cells induces the rapid ATM (ataxia telangiectasia mutated)/ATR (ataxia telangiectasia and Rad3 related)-dependent phosphorylation of histone H2AX (γ-H2AX). In budding yeast, a single endonuclease-induced DSB triggers γ-H2AX modification of 50 kb on either side of the DSB. The extent of γ-H2AX spreading does not depend on the chromosomal sequences. DNA resection after DSB formation causes the slow, progressive loss of γ-H2AX from single-stranded DNA and, after several hours, the Mec1 (ATR)-dependent spreading of γ-H2AX to more distant regions. Heterochromatic sequences are only weakly modified upon insertion of a 3-kb silent HMR locus into a γ-H2AX–covered region. The presence of heterochromatin does not stop the phosphorylation of chromatin more distant from the DSB. In mouse embryo fibroblasts, γ-H2AX distribution shows that γ-H2AX foci increase in size as chromatin becomes more accessible. In yeast, we see a high level of constitutive γ-H2AX in telomere regions in the absence of any exogenous DNA damage, suggesting that yeast chromosome ends are transiently detected as DSBs.
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16 July 2007
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July 16 2007
Heterochromatin is refractory to γ-H2AX modification in yeast and mammals
Jung-Ae Kim,
Jung-Ae Kim
1Rosenstiel Center
2Department of Biology, Brandeis University, Waltham, MA 02454
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Michael Kruhlak,
Michael Kruhlak
3Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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Farokh Dotiwala,
Farokh Dotiwala
1Rosenstiel Center
2Department of Biology, Brandeis University, Waltham, MA 02454
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André Nussenzweig,
André Nussenzweig
3Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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James E. Haber
James E. Haber
1Rosenstiel Center
2Department of Biology, Brandeis University, Waltham, MA 02454
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Jung-Ae Kim
1Rosenstiel Center
2Department of Biology, Brandeis University, Waltham, MA 02454
Michael Kruhlak
3Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Farokh Dotiwala
1Rosenstiel Center
2Department of Biology, Brandeis University, Waltham, MA 02454
André Nussenzweig
3Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
James E. Haber
1Rosenstiel Center
2Department of Biology, Brandeis University, Waltham, MA 02454
Correspondence to James E. Haber: [email protected]
Abbreviations used in this paper: ChIP, chromatin immunoprecipitation; CPY, carboxy peptidase Y; DSB, double-strand break; MMS, methylmethanesulfonate; NCS, neocarzinostatin; TPE, telomere position effect; TSA, trichostatin A.
Received:
December 06 2006
Accepted:
June 15 2007
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2007
J Cell Biol (2007) 178 (2): 209–218.
Article history
Received:
December 06 2006
Accepted:
June 15 2007
Citation
Jung-Ae Kim, Michael Kruhlak, Farokh Dotiwala, André Nussenzweig, James E. Haber; Heterochromatin is refractory to γ-H2AX modification in yeast and mammals . J Cell Biol 16 July 2007; 178 (2): 209–218. doi: https://doi.org/10.1083/jcb.200612031
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