UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide
| Autor: | Andrés Aguilera, Xiaoyu Xue, Patrick Sung, Víctor M. González-Basallote, Sonia Barroso, Sergio Muñoz, Carmen Pérez-Calero, Aleix Bayona-Feliu |
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| Přispěvatelé: | Universidad de Sevilla. Departamento de Genética |
| Rok vydání: | 2020 |
| Předmět: |
Genome instability
Double-strand breaks UAP56/DDX39B THO complex R loops Biology RNA–DNA helicase Genome 03 medical and health sciences 0302 clinical medicine Transcription (biology) Replication fork stalling Genetics RNA–DNA hybrids 030304 developmental biology 0303 health sciences Helicase RNA 3. Good health Chromatin Cell biology Histone 030220 oncology & carcinogenesis biology.protein Developmental Biology |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname idUS: Depósito de Investigación de la Universidad de Sevilla Universidad de Sevilla (US) Genes & Development idUS. Depósito de Investigación de la Universidad de Sevilla |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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