R loops: new modulators of genome dynamics and function

Nat Rev Genet. 2015 Oct;16(10):583-97. doi: 10.1038/nrg3961. Epub 2015 Sep 15.


R loops are nucleic acid structures composed of an RNA-DNA hybrid and a displaced single-stranded DNA. Recently, evidence has emerged that R loops occur more often in the genome and have greater physiological relevance, including roles in transcription and chromatin structure, than was previously predicted. Importantly, however, R loops are also a major threat to genome stability. For this reason, several DNA and RNA metabolism factors prevent R-loop formation in cells. Dysfunction of these factors causes R-loop accumulation, which leads to replication stress, genome instability, chromatin alterations or gene silencing, phenomena that are frequently associated with cancer and a number of genetic diseases. We review the current knowledge of the mechanisms controlling R loops and their putative relationship with disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chromatin / metabolism
  • DNA / chemistry*
  • DNA / genetics
  • DNA / metabolism
  • DNA, Single-Stranded / metabolism
  • Genomic Instability
  • Humans
  • Neoplasms / genetics
  • Neurodegenerative Diseases / genetics
  • Nucleic Acid Conformation
  • RNA / chemistry*
  • RNA / genetics
  • RNA / metabolism
  • RNA Polymerase II / metabolism
  • Transcription, Genetic


  • Chromatin
  • DNA, Single-Stranded
  • RNA
  • DNA
  • RNA Polymerase II