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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...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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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. |
format | Text |
id | pubmed-2064441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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