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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...

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Autores principales: Pérez-Calero, Carmen, Bayona-Feliu, Aleix, Xue, Xiaoyu, Barroso, Sonia I., Muñoz, Sergio, González-Basallote, Víctor M., Sung, Patrick, Aguilera, Andrés
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2020
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.
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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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