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Functional interplay between Mediator and RNA polymerase II in Rad2/XPG loading to the chromatin
Transcription and maintenance of genome integrity are fundamental cellular functions. Deregulation of transcription and defects in DNA repair lead to serious pathologies. The Mediator complex links RNA polymerase (Pol) II transcription and nucleotide excision repair via Rad2/XPG endonuclease. Howeve...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753472/ https://www.ncbi.nlm.nih.gov/pubmed/31299084 http://dx.doi.org/10.1093/nar/gkz598 |
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author | Georges, Adrien Gopaul, Diyavarshini Denby Wilkes, Cyril Giordanengo Aiach, Nathalie Novikova, Elizaveta Barrault, Marie-Bénédicte Alibert, Olivier Soutourina, Julie |
author_facet | Georges, Adrien Gopaul, Diyavarshini Denby Wilkes, Cyril Giordanengo Aiach, Nathalie Novikova, Elizaveta Barrault, Marie-Bénédicte Alibert, Olivier Soutourina, Julie |
author_sort | Georges, Adrien |
collection | PubMed |
description | Transcription and maintenance of genome integrity are fundamental cellular functions. Deregulation of transcription and defects in DNA repair lead to serious pathologies. The Mediator complex links RNA polymerase (Pol) II transcription and nucleotide excision repair via Rad2/XPG endonuclease. However, the functional interplay between Rad2/XPG, Mediator and Pol II remains to be determined. In this study, we investigated their functional dynamics using genomic and genetic approaches. In a mutant affected in Pol II phosphorylation leading to Mediator stabilization on core promoters, Rad2 genome-wide occupancy shifts towards core promoters following that of Mediator, but decreases on transcribed regions together with Pol II. Specific Mediator mutations increase UV sensitivity, reduce Rad2 recruitment to transcribed regions, lead to uncoupling of Rad2, Mediator and Pol II and to colethality with deletion of Rpb9 Pol II subunit involved in transcription-coupled repair. We provide new insights into the functional interplay between Rad2, Mediator and Pol II and propose that dynamic interactions with Mediator and Pol II are involved in Rad2 loading to the chromatin. Our work contributes to the understanding of the complex link between transcription and DNA repair machineries, dysfunction of which leads to severe diseases. |
format | Online Article Text |
id | pubmed-6753472 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-67534722019-09-25 Functional interplay between Mediator and RNA polymerase II in Rad2/XPG loading to the chromatin Georges, Adrien Gopaul, Diyavarshini Denby Wilkes, Cyril Giordanengo Aiach, Nathalie Novikova, Elizaveta Barrault, Marie-Bénédicte Alibert, Olivier Soutourina, Julie Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Transcription and maintenance of genome integrity are fundamental cellular functions. Deregulation of transcription and defects in DNA repair lead to serious pathologies. The Mediator complex links RNA polymerase (Pol) II transcription and nucleotide excision repair via Rad2/XPG endonuclease. However, the functional interplay between Rad2/XPG, Mediator and Pol II remains to be determined. In this study, we investigated their functional dynamics using genomic and genetic approaches. In a mutant affected in Pol II phosphorylation leading to Mediator stabilization on core promoters, Rad2 genome-wide occupancy shifts towards core promoters following that of Mediator, but decreases on transcribed regions together with Pol II. Specific Mediator mutations increase UV sensitivity, reduce Rad2 recruitment to transcribed regions, lead to uncoupling of Rad2, Mediator and Pol II and to colethality with deletion of Rpb9 Pol II subunit involved in transcription-coupled repair. We provide new insights into the functional interplay between Rad2, Mediator and Pol II and propose that dynamic interactions with Mediator and Pol II are involved in Rad2 loading to the chromatin. Our work contributes to the understanding of the complex link between transcription and DNA repair machineries, dysfunction of which leads to severe diseases. Oxford University Press 2019-09-26 2019-07-12 /pmc/articles/PMC6753472/ /pubmed/31299084 http://dx.doi.org/10.1093/nar/gkz598 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Georges, Adrien Gopaul, Diyavarshini Denby Wilkes, Cyril Giordanengo Aiach, Nathalie Novikova, Elizaveta Barrault, Marie-Bénédicte Alibert, Olivier Soutourina, Julie Functional interplay between Mediator and RNA polymerase II in Rad2/XPG loading to the chromatin |
title | Functional interplay between Mediator and RNA polymerase II in Rad2/XPG loading to the chromatin |
title_full | Functional interplay between Mediator and RNA polymerase II in Rad2/XPG loading to the chromatin |
title_fullStr | Functional interplay between Mediator and RNA polymerase II in Rad2/XPG loading to the chromatin |
title_full_unstemmed | Functional interplay between Mediator and RNA polymerase II in Rad2/XPG loading to the chromatin |
title_short | Functional interplay between Mediator and RNA polymerase II in Rad2/XPG loading to the chromatin |
title_sort | functional interplay between mediator and rna polymerase ii in rad2/xpg loading to the chromatin |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753472/ https://www.ncbi.nlm.nih.gov/pubmed/31299084 http://dx.doi.org/10.1093/nar/gkz598 |
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