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Senataxin controls meiotic silencing through ATR activation and chromatin remodeling
Senataxin, defective in ataxia oculomotor apraxia type 2, protects the genome by facilitating the resolution of RNA–DNA hybrids (R-loops) and other aspects of RNA processing. Disruption of this gene in mice causes failure of meiotic recombination and defective meiotic sex chromosome inactivation, le...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860845/ https://www.ncbi.nlm.nih.gov/pubmed/27462424 http://dx.doi.org/10.1038/celldisc.2015.25 |
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author | Yeo, Abrey J Becherel, Olivier J Luff, John E Graham, Mark E Richard, Derek Lavin, Martin F |
author_facet | Yeo, Abrey J Becherel, Olivier J Luff, John E Graham, Mark E Richard, Derek Lavin, Martin F |
author_sort | Yeo, Abrey J |
collection | PubMed |
description | Senataxin, defective in ataxia oculomotor apraxia type 2, protects the genome by facilitating the resolution of RNA–DNA hybrids (R-loops) and other aspects of RNA processing. Disruption of this gene in mice causes failure of meiotic recombination and defective meiotic sex chromosome inactivation, leading to male infertility. Here we provide evidence that the disruption of Setx leads to reduced SUMOylation and disruption of protein localization across the XY body during meiosis. We demonstrate that senataxin and other DNA damage repair proteins, including ataxia telangiectasia and Rad3-related protein-interacting partner, are SUMOylated, and a marked downregulation of both ataxia telangiectasia and Rad3-related protein-interacting partner and TopBP1 leading to defective activation and signaling through ataxia telangiectasia and Rad3-related protein occurs in the absence of senataxin. Furthermore, chromodomain helicase DNA-binding protein 4, a component of the nucleosome remodeling and deacetylase chromatin remodeler that interacts with both ataxia telangiectasia and Rad3-related protein and senataxin was not recruited efficiently to the XY body, triggering altered histone acetylation and chromatin conformation in Setx(−/−) pachytene-staged spermatocytes. These results demonstrate that senataxin has a critical role in ataxia telangiectasia and Rad3-related protein- and chromodomain helicase DNA-binding protein 4-mediated transcriptional silencing and chromatin remodeling during meiosis providing greater insight into its critical role in gene regulation to protect against neurodegeneration. |
format | Online Article Text |
id | pubmed-4860845 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48608452016-07-26 Senataxin controls meiotic silencing through ATR activation and chromatin remodeling Yeo, Abrey J Becherel, Olivier J Luff, John E Graham, Mark E Richard, Derek Lavin, Martin F Cell Discov Article Senataxin, defective in ataxia oculomotor apraxia type 2, protects the genome by facilitating the resolution of RNA–DNA hybrids (R-loops) and other aspects of RNA processing. Disruption of this gene in mice causes failure of meiotic recombination and defective meiotic sex chromosome inactivation, leading to male infertility. Here we provide evidence that the disruption of Setx leads to reduced SUMOylation and disruption of protein localization across the XY body during meiosis. We demonstrate that senataxin and other DNA damage repair proteins, including ataxia telangiectasia and Rad3-related protein-interacting partner, are SUMOylated, and a marked downregulation of both ataxia telangiectasia and Rad3-related protein-interacting partner and TopBP1 leading to defective activation and signaling through ataxia telangiectasia and Rad3-related protein occurs in the absence of senataxin. Furthermore, chromodomain helicase DNA-binding protein 4, a component of the nucleosome remodeling and deacetylase chromatin remodeler that interacts with both ataxia telangiectasia and Rad3-related protein and senataxin was not recruited efficiently to the XY body, triggering altered histone acetylation and chromatin conformation in Setx(−/−) pachytene-staged spermatocytes. These results demonstrate that senataxin has a critical role in ataxia telangiectasia and Rad3-related protein- and chromodomain helicase DNA-binding protein 4-mediated transcriptional silencing and chromatin remodeling during meiosis providing greater insight into its critical role in gene regulation to protect against neurodegeneration. Nature Publishing Group 2015-09-29 /pmc/articles/PMC4860845/ /pubmed/27462424 http://dx.doi.org/10.1038/celldisc.2015.25 Text en Copyright © 2015 SIBS, CAS http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Yeo, Abrey J Becherel, Olivier J Luff, John E Graham, Mark E Richard, Derek Lavin, Martin F Senataxin controls meiotic silencing through ATR activation and chromatin remodeling |
title | Senataxin controls meiotic silencing through ATR activation and chromatin remodeling |
title_full | Senataxin controls meiotic silencing through ATR activation and chromatin remodeling |
title_fullStr | Senataxin controls meiotic silencing through ATR activation and chromatin remodeling |
title_full_unstemmed | Senataxin controls meiotic silencing through ATR activation and chromatin remodeling |
title_short | Senataxin controls meiotic silencing through ATR activation and chromatin remodeling |
title_sort | senataxin controls meiotic silencing through atr activation and chromatin remodeling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860845/ https://www.ncbi.nlm.nih.gov/pubmed/27462424 http://dx.doi.org/10.1038/celldisc.2015.25 |
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