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UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide
Nonscheduled R loops represent a major source of DNA damage and replication stress. Cells have different ways to prevent R-loop accumulation. One mechanism relies on the conserved THO complex in association with cotranscriptional RNA processing factors including the RNA-dependent ATPase UAP56/DDX39B...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328515/ https://www.ncbi.nlm.nih.gov/pubmed/32439635 http://dx.doi.org/10.1101/gad.336024.119 |
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author | Pérez-Calero, Carmen Bayona-Feliu, Aleix Xue, Xiaoyu Barroso, Sonia I. Muñoz, Sergio González-Basallote, Víctor M. Sung, Patrick Aguilera, Andrés |
author_facet | Pérez-Calero, Carmen Bayona-Feliu, Aleix Xue, Xiaoyu Barroso, Sonia I. Muñoz, Sergio González-Basallote, Víctor M. Sung, Patrick Aguilera, Andrés |
author_sort | Pérez-Calero, Carmen |
collection | PubMed |
description | Nonscheduled R loops represent a major source of DNA damage and replication stress. Cells have different ways to prevent R-loop accumulation. One mechanism relies on the conserved THO complex in association with cotranscriptional RNA processing factors including the RNA-dependent ATPase UAP56/DDX39B and histone modifiers such as the SIN3 deacetylase in humans. We investigated the function of UAP56/DDX39B in R-loop removal. We show that UAP56 depletion causes R-loop accumulation, R-loop-mediated genome instability, and replication fork stalling. We demonstrate an RNA–DNA helicase activity in UAP56 and show that its overexpression suppresses R loops and genome instability induced by depleting five different unrelated factors. UAP56/DDX39B localizes to active chromatin and prevents the accumulation of RNA–DNA hybrids over the entire genome. We propose that, in addition to its RNA processing role, UAP56/DDX39B is a key helicase required to eliminate harmful cotranscriptional RNA structures that otherwise would block transcription and replication. |
format | Online Article Text |
id | pubmed-7328515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-73285152021-01-01 UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide Pérez-Calero, Carmen Bayona-Feliu, Aleix Xue, Xiaoyu Barroso, Sonia I. Muñoz, Sergio González-Basallote, Víctor M. Sung, Patrick Aguilera, Andrés Genes Dev Research Paper Nonscheduled R loops represent a major source of DNA damage and replication stress. Cells have different ways to prevent R-loop accumulation. One mechanism relies on the conserved THO complex in association with cotranscriptional RNA processing factors including the RNA-dependent ATPase UAP56/DDX39B and histone modifiers such as the SIN3 deacetylase in humans. We investigated the function of UAP56/DDX39B in R-loop removal. We show that UAP56 depletion causes R-loop accumulation, R-loop-mediated genome instability, and replication fork stalling. We demonstrate an RNA–DNA helicase activity in UAP56 and show that its overexpression suppresses R loops and genome instability induced by depleting five different unrelated factors. UAP56/DDX39B localizes to active chromatin and prevents the accumulation of RNA–DNA hybrids over the entire genome. We propose that, in addition to its RNA processing role, UAP56/DDX39B is a key helicase required to eliminate harmful cotranscriptional RNA structures that otherwise would block transcription and replication. Cold Spring Harbor Laboratory Press 2020-07-01 /pmc/articles/PMC7328515/ /pubmed/32439635 http://dx.doi.org/10.1101/gad.336024.119 Text en © 2020 Pérez-Calero et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper Pérez-Calero, Carmen Bayona-Feliu, Aleix Xue, Xiaoyu Barroso, Sonia I. Muñoz, Sergio González-Basallote, Víctor M. Sung, Patrick Aguilera, Andrés UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide |
title | UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide |
title_full | UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide |
title_fullStr | UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide |
title_full_unstemmed | UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide |
title_short | UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide |
title_sort | uap56/ddx39b is a major cotranscriptional rna–dna helicase that unwinds harmful r loops genome-wide |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328515/ https://www.ncbi.nlm.nih.gov/pubmed/32439635 http://dx.doi.org/10.1101/gad.336024.119 |
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