UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide

Carmen Pérez-Calero, Aleix Bayona-Feliu, Xiaoyu Xue, Sonia I. Barroso, Sergio Muñoz, Víctor M. González-Basallote, Patrick Sung, Andrés Aguilera

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalGenes and Development
Volume34
Issue number13-14
DOIs
StatePublished - Jul 2020

Keywords

  • Double-strand breaks
  • Genome instability
  • R loops
  • RNA–DNA helicase
  • RNA–DNA hybrids
  • Replication fork stalling
  • UAP56/DDX39B

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Pérez-Calero, C., Bayona-Feliu, A., Xue, X., Barroso, S. I., Muñoz, S., González-Basallote, V. M., Sung, P., & Aguilera, A. (2020). UAP56/DDX39B is a major cotranscriptional RNA–DNA helicase that unwinds harmful R loops genome-wide. Genes and Development, 34(13-14), 1-15. https://doi.org/10.1101/GAD.336024.119