@article{52e55f022dc644c99125d4c185f78f38,
title = "UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide",
abstract = "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.",
keywords = "Double-strand breaks, Genome instability, R loops, RNA–DNA helicase, RNA–DNA hybrids, Replication fork stalling, UAP56/DDX39B",
author = "Carmen P{\'e}rez-Calero and Aleix Bayona-Feliu and Xiaoyu Xue and Barroso, {Sonia I.} and Sergio Mu{\~n}oz and Gonz{\'a}lez-Basallote, {V{\'i}ctor M.} and Patrick Sung and Andr{\'e}s Aguilera",
note = "Funding Information: We thank Arijit Dutta for his help with the in vitro assay, and Eloisa And{\'u}jar and M{\'o}nica P{\'e}rez (CABIMER{\textquoteright}s Genomic Unit) for DNA sequencing service. WT and helicase-dead UAP56 plasmids for in vitro experiments were a gift from Rui Zhao (University of Colorado, Denver). pUBC-EGFP-UAP56 was a gift from Sonia Silva (A.A.{\textquoteright}s laboratory). Research in A.A.{\textquoteright}s laboratory was funded by the European Research Council (grant ERC2014 AdG669898 TARLOOP), the Spanish Ministry of Economy and Competitiveness (grants BFU2013-42918-P and BFU2016-75058-P), and the European Union (FEDER). P.S. and X.X. were supported by National Institutes of Health grants R35 CA241801 and R21 ES028792, respectively. A.B.-F. was supported by a Juan de la Cierva postdoctoral contract from the Spanish Ministry of Science and Innovation. Funding Information: We thank Arijit Dutta for his help with the in vitro assay, and Eloisa And?jar and M?nica P?rez (CABIMER?s Genomic Unit) for DNA sequencing service. WT and helicase-dead UAP56 plasmids for in vitro experiments were a gift from Rui Zhao (University of Colorado, Denver). pUBC-EGFP-UAP56 was a gift from Sonia Silva (A.A.?s laboratory). Research in A.A.?s laboratory was funded by the European Research Council (grant ERC2014 AdG669898 TARLOOP), the Spanish Ministry of Economy and Competitiveness (grants BFU2013-42918-P and BFU2016-75058-P), and the European Union (FEDER). P.S. and X.X. were supported by National Institutes of Health grants R35 CA241801 and R21 ES028792, respectively. A.B.-F. was supported by a Juan de la Cierva postdoctoral contract from the Spanish Ministry of Science and Innovation. Publisher Copyright: {\textcopyright} 2020 P{\'e}rez-Calero et al.",
year = "2020",
month = jul,
doi = "10.1101/GAD.336024.119",
language = "English (US)",
volume = "34",
pages = "898--912",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "13-14",
}