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Heterochromatin is refractory to γ-H2AX modification in yeast and mammals

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...

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Autores principales: Kim, Jung-Ae, Kruhlak, Michael, Dotiwala, Farokh, Nussenzweig, André, Haber, James E.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064441/
https://www.ncbi.nlm.nih.gov/pubmed/17635934
http://dx.doi.org/10.1083/jcb.200612031
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author Kim, Jung-Ae
Kruhlak, Michael
Dotiwala, Farokh
Nussenzweig, André
Haber, James E.
author_facet Kim, Jung-Ae
Kruhlak, Michael
Dotiwala, Farokh
Nussenzweig, André
Haber, James E.
author_sort Kim, Jung-Ae
collection PubMed
description 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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spelling pubmed-20644412008-01-16 Heterochromatin is refractory to γ-H2AX modification in yeast and mammals Kim, Jung-Ae Kruhlak, Michael Dotiwala, Farokh Nussenzweig, André Haber, James E. J Cell Biol Research Articles 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. The Rockefeller University Press 2007-07-16 /pmc/articles/PMC2064441/ /pubmed/17635934 http://dx.doi.org/10.1083/jcb.200612031 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Kim, Jung-Ae
Kruhlak, Michael
Dotiwala, Farokh
Nussenzweig, André
Haber, James E.
Heterochromatin is refractory to γ-H2AX modification in yeast and mammals
title Heterochromatin is refractory to γ-H2AX modification in yeast and mammals
title_full Heterochromatin is refractory to γ-H2AX modification in yeast and mammals
title_fullStr Heterochromatin is refractory to γ-H2AX modification in yeast and mammals
title_full_unstemmed Heterochromatin is refractory to γ-H2AX modification in yeast and mammals
title_short Heterochromatin is refractory to γ-H2AX modification in yeast and mammals
title_sort heterochromatin is refractory to γ-h2ax modification in yeast and mammals
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064441/
https://www.ncbi.nlm.nih.gov/pubmed/17635934
http://dx.doi.org/10.1083/jcb.200612031
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