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Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks

The repair of DNA double-strand breaks (DSBs) is facilitated by the phosphorylation of H2AX, which organizes DNA damage signaling and chromatin remodeling complexes in the vicinity of the lesion (Pilch, D.R., O.A. Sedelnikova, C. Redon, A. Celeste, A. Nussenzweig, and W.M. Bonner. 2003. Biochem. Cel...

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Autores principales: Kruhlak, Michael J., Celeste, Arkady, Dellaire, Graham, Fernandez-Capetillo, Oscar, Müller, Waltraud G., McNally, James G., Bazett-Jones, David P., Nussenzweig, André
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063727/
https://www.ncbi.nlm.nih.gov/pubmed/16520385
http://dx.doi.org/10.1083/jcb.200510015
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author Kruhlak, Michael J.
Celeste, Arkady
Dellaire, Graham
Fernandez-Capetillo, Oscar
Müller, Waltraud G.
McNally, James G.
Bazett-Jones, David P.
Nussenzweig, André
author_facet Kruhlak, Michael J.
Celeste, Arkady
Dellaire, Graham
Fernandez-Capetillo, Oscar
Müller, Waltraud G.
McNally, James G.
Bazett-Jones, David P.
Nussenzweig, André
author_sort Kruhlak, Michael J.
collection PubMed
description The repair of DNA double-strand breaks (DSBs) is facilitated by the phosphorylation of H2AX, which organizes DNA damage signaling and chromatin remodeling complexes in the vicinity of the lesion (Pilch, D.R., O.A. Sedelnikova, C. Redon, A. Celeste, A. Nussenzweig, and W.M. Bonner. 2003. Biochem. Cell Biol. 81:123–129; Morrison, A.J., and X. Shen. 2005. Cell Cycle. 4:568–571; van Attikum, H., and S.M. Gasser. 2005. Nat. Rev. Mol. Cell. Biol. 6:757–765). The disruption of DNA integrity induces an alteration of chromatin architecture that has been proposed to activate the DNA damage transducing kinase ataxia telangiectasia mutated (ATM; Bakkenist, C.J., and M.B. Kastan. 2003. Nature. 421:499–506). However, little is known about the physical properties of damaged chromatin. In this study, we use a photoactivatable version of GFP-tagged histone H2B to examine the mobility and structure of chromatin containing DSBs in living cells. We find that chromatin containing DSBs exhibits limited mobility but undergoes an energy-dependent local expansion immediately after DNA damage. The localized expansion observed in real time corresponds to a 30–40% reduction in the density of chromatin fibers in the vicinity of DSBs, as measured by energy-filtering transmission electron microscopy. The observed opening of chromatin occurs independently of H2AX and ATM. We propose that localized adenosine triphosphate–dependent decondensation of chromatin at DSBs establishes an accessible subnuclear environment that facilitates DNA damage signaling and repair.
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spelling pubmed-20637272007-11-29 Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks Kruhlak, Michael J. Celeste, Arkady Dellaire, Graham Fernandez-Capetillo, Oscar Müller, Waltraud G. McNally, James G. Bazett-Jones, David P. Nussenzweig, André J Cell Biol Research Articles The repair of DNA double-strand breaks (DSBs) is facilitated by the phosphorylation of H2AX, which organizes DNA damage signaling and chromatin remodeling complexes in the vicinity of the lesion (Pilch, D.R., O.A. Sedelnikova, C. Redon, A. Celeste, A. Nussenzweig, and W.M. Bonner. 2003. Biochem. Cell Biol. 81:123–129; Morrison, A.J., and X. Shen. 2005. Cell Cycle. 4:568–571; van Attikum, H., and S.M. Gasser. 2005. Nat. Rev. Mol. Cell. Biol. 6:757–765). The disruption of DNA integrity induces an alteration of chromatin architecture that has been proposed to activate the DNA damage transducing kinase ataxia telangiectasia mutated (ATM; Bakkenist, C.J., and M.B. Kastan. 2003. Nature. 421:499–506). However, little is known about the physical properties of damaged chromatin. In this study, we use a photoactivatable version of GFP-tagged histone H2B to examine the mobility and structure of chromatin containing DSBs in living cells. We find that chromatin containing DSBs exhibits limited mobility but undergoes an energy-dependent local expansion immediately after DNA damage. The localized expansion observed in real time corresponds to a 30–40% reduction in the density of chromatin fibers in the vicinity of DSBs, as measured by energy-filtering transmission electron microscopy. The observed opening of chromatin occurs independently of H2AX and ATM. We propose that localized adenosine triphosphate–dependent decondensation of chromatin at DSBs establishes an accessible subnuclear environment that facilitates DNA damage signaling and repair. The Rockefeller University Press 2006-03-13 /pmc/articles/PMC2063727/ /pubmed/16520385 http://dx.doi.org/10.1083/jcb.200510015 Text en Copyright © 2006, 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
Kruhlak, Michael J.
Celeste, Arkady
Dellaire, Graham
Fernandez-Capetillo, Oscar
Müller, Waltraud G.
McNally, James G.
Bazett-Jones, David P.
Nussenzweig, André
Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks
title Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks
title_full Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks
title_fullStr Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks
title_full_unstemmed Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks
title_short Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks
title_sort changes in chromatin structure and mobility in living cells at sites of dna double-strand breaks
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063727/
https://www.ncbi.nlm.nih.gov/pubmed/16520385
http://dx.doi.org/10.1083/jcb.200510015
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