UAP56/DDX39B is a major cotranscriptional RNA-DNA helicase that unwinds harmful R loops genome-wide.
R loops
RNA–DNA helicase
RNA–DNA hybrids
UAP56/DDX39B
double-strand breaks
genome instability
replication fork stalling
Journal
Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
13
12
2019
accepted:
20
04
2020
pubmed:
23
5
2020
medline:
11
11
2020
entrez:
23
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32439635
pii: gad.336024.119
doi: 10.1101/gad.336024.119
pmc: PMC7328515
doi:
Substances chimiques
Chromatin
0
DDX39B protein, human
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
898-912Subventions
Organisme : NIEHS NIH HHS
ID : R21 ES028792
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA241801
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2020 Pérez-Calero et al.; Published by Cold Spring Harbor Laboratory Press.
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