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Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks

Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of γH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further...

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Autores principales: Caron, Pierre, Aymard, Francois, Iacovoni, Jason S., Briois, Sébastien, Canitrot, Yvan, Bugler, Beatrix, Massip, Laurent, Losada, Ana, Legube, Gaëlle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261922/
https://www.ncbi.nlm.nih.gov/pubmed/22275873
http://dx.doi.org/10.1371/journal.pgen.1002460
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author Caron, Pierre
Aymard, Francois
Iacovoni, Jason S.
Briois, Sébastien
Canitrot, Yvan
Bugler, Beatrix
Massip, Laurent
Losada, Ana
Legube, Gaëlle
author_facet Caron, Pierre
Aymard, Francois
Iacovoni, Jason S.
Briois, Sébastien
Canitrot, Yvan
Bugler, Beatrix
Massip, Laurent
Losada, Ana
Legube, Gaëlle
author_sort Caron, Pierre
collection PubMed
description Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of γH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit of the cohesin complex, previously characterized as required for repair by homologous recombination. We found that recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs in human cells. In addition, we show that cohesin controls γH2AX distribution within domains. Indeed, as we reported previously for transcription, cohesin binding antagonizes γH2AX spreading. Remarkably, depletion of cohesin leads to an increase of γH2AX at cohesin-bound genes, associated with a decrease in their expression level after DSB induction. We propose that, in agreement with their function in chromosome architecture, cohesin could also help to isolate active genes from some chromatin remodelling and modifications such as the ones that occur when a DSB is detected on the genome.
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spelling pubmed-32619222012-01-24 Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks Caron, Pierre Aymard, Francois Iacovoni, Jason S. Briois, Sébastien Canitrot, Yvan Bugler, Beatrix Massip, Laurent Losada, Ana Legube, Gaëlle PLoS Genet Research Article Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of γH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit of the cohesin complex, previously characterized as required for repair by homologous recombination. We found that recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs in human cells. In addition, we show that cohesin controls γH2AX distribution within domains. Indeed, as we reported previously for transcription, cohesin binding antagonizes γH2AX spreading. Remarkably, depletion of cohesin leads to an increase of γH2AX at cohesin-bound genes, associated with a decrease in their expression level after DSB induction. We propose that, in agreement with their function in chromosome architecture, cohesin could also help to isolate active genes from some chromatin remodelling and modifications such as the ones that occur when a DSB is detected on the genome. Public Library of Science 2012-01-19 /pmc/articles/PMC3261922/ /pubmed/22275873 http://dx.doi.org/10.1371/journal.pgen.1002460 Text en Caron et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Caron, Pierre
Aymard, Francois
Iacovoni, Jason S.
Briois, Sébastien
Canitrot, Yvan
Bugler, Beatrix
Massip, Laurent
Losada, Ana
Legube, Gaëlle
Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks
title Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks
title_full Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks
title_fullStr Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks
title_full_unstemmed Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks
title_short Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks
title_sort cohesin protects genes against γh2ax induced by dna double-strand breaks
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261922/
https://www.ncbi.nlm.nih.gov/pubmed/22275873
http://dx.doi.org/10.1371/journal.pgen.1002460
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