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DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing
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DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing
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DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing
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Journal Article
DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing
2018
Overview
R-loops are stable nucleic acid structures that have important physiological functions, but which also pose a significant threat to genomic stability. Increased R-loops cause replication stress and chromosome fragility and have been associated with diseases such as neurodegeneration and cancer. Although excessive R-loops are a feature of cells that are defective in RNA processing, what causes them to form is unclear. Here, we demonstrate that DHX9 (RNA helicase A) promotes the formation of pathological and non-pathological R-loops. In the absence of splicing factors, formation of R-loops correlates with the prolonged association of DHX9 with RNA Polymerase II (RNA Pol II). This leads to the production of DNA–RNA hybrid, which traps RNA Pol II on chromatin with the potential to block DNA replication. Our data provide a molecular mechanism for the formation of R-loops that is relevant to neurodegenerative diseases and cancers in which deregulated RNA processing is a feature.
Unresolved R-loops can represent a threat to genome stability. Here the authors reveal that DHX9 helicase can promote R-loop formation in the absence of splicing factors SFPQ and SF3B3.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/31
/ 13/89
/ 14
/ 14/34
/ 82/1
/ 82/80
/ Cancer
/ DEAD-box RNA Helicases - chemistry
/ DEAD-box RNA Helicases - physiology
/ DNA
/ DNA Replication - physiology
/ Genes
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Neoplasm Proteins - chemistry
/ Neoplasm Proteins - physiology
/ Proteins
/ R-loops
/ RNA
/ RNA Polymerase II - chemistry
/ RNA Polymerase II - metabolism
/ RNA Polymerase II - physiology
/ RNA Splicing Factors - chemistry
/ RNA Splicing Factors - metabolism
/ Science
/ Splicing
