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Histone demethylase KDM5A regulates the ZMYND8–NuRD chromatin remodeler to promote DNA repair
Upon DNA damage, histone modifications are dynamically reshaped to accommodate DNA damage signaling and repair within chromatin. In this study, we report the identification of the histone demethylase KDM5A as a key regulator of the bromodomain protein ZMYND8 and NuRD (nucleosome remodeling and histo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496618/ https://www.ncbi.nlm.nih.gov/pubmed/28572115 http://dx.doi.org/10.1083/jcb.201611135 |
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author | Gong, Fade Clouaire, Thomas Aguirrebengoa, Marion Legube, Gaëlle Miller, Kyle M. |
author_facet | Gong, Fade Clouaire, Thomas Aguirrebengoa, Marion Legube, Gaëlle Miller, Kyle M. |
author_sort | Gong, Fade |
collection | PubMed |
description | Upon DNA damage, histone modifications are dynamically reshaped to accommodate DNA damage signaling and repair within chromatin. In this study, we report the identification of the histone demethylase KDM5A as a key regulator of the bromodomain protein ZMYND8 and NuRD (nucleosome remodeling and histone deacetylation) complex in the DNA damage response. We observe KDM5A-dependent H3K4me3 demethylation within chromatin near DNA double-strand break (DSB) sites. Mechanistically, demethylation of H3K4me3 is required for ZMYND8–NuRD binding to chromatin and recruitment to DNA damage. Functionally, KDM5A deficiency results in impaired transcriptional silencing and repair of DSBs by homologous recombination. Thus, this study identifies a crucial function for KDM5A in demethylating H3K4 to allow ZMYND8–NuRD to operate within damaged chromatin to repair DSBs. |
format | Online Article Text |
id | pubmed-5496618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-54966182018-01-03 Histone demethylase KDM5A regulates the ZMYND8–NuRD chromatin remodeler to promote DNA repair Gong, Fade Clouaire, Thomas Aguirrebengoa, Marion Legube, Gaëlle Miller, Kyle M. J Cell Biol Research Articles Upon DNA damage, histone modifications are dynamically reshaped to accommodate DNA damage signaling and repair within chromatin. In this study, we report the identification of the histone demethylase KDM5A as a key regulator of the bromodomain protein ZMYND8 and NuRD (nucleosome remodeling and histone deacetylation) complex in the DNA damage response. We observe KDM5A-dependent H3K4me3 demethylation within chromatin near DNA double-strand break (DSB) sites. Mechanistically, demethylation of H3K4me3 is required for ZMYND8–NuRD binding to chromatin and recruitment to DNA damage. Functionally, KDM5A deficiency results in impaired transcriptional silencing and repair of DSBs by homologous recombination. Thus, this study identifies a crucial function for KDM5A in demethylating H3K4 to allow ZMYND8–NuRD to operate within damaged chromatin to repair DSBs. The Rockefeller University Press 2017-07-03 /pmc/articles/PMC5496618/ /pubmed/28572115 http://dx.doi.org/10.1083/jcb.201611135 Text en © 2017 Gong et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Gong, Fade Clouaire, Thomas Aguirrebengoa, Marion Legube, Gaëlle Miller, Kyle M. Histone demethylase KDM5A regulates the ZMYND8–NuRD chromatin remodeler to promote DNA repair |
title | Histone demethylase KDM5A regulates the ZMYND8–NuRD chromatin remodeler to promote DNA repair |
title_full | Histone demethylase KDM5A regulates the ZMYND8–NuRD chromatin remodeler to promote DNA repair |
title_fullStr | Histone demethylase KDM5A regulates the ZMYND8–NuRD chromatin remodeler to promote DNA repair |
title_full_unstemmed | Histone demethylase KDM5A regulates the ZMYND8–NuRD chromatin remodeler to promote DNA repair |
title_short | Histone demethylase KDM5A regulates the ZMYND8–NuRD chromatin remodeler to promote DNA repair |
title_sort | histone demethylase kdm5a regulates the zmynd8–nurd chromatin remodeler to promote dna repair |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496618/ https://www.ncbi.nlm.nih.gov/pubmed/28572115 http://dx.doi.org/10.1083/jcb.201611135 |
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