R Loops: From Physiological to Pathological Roles

Cell. 2019 Oct 17;179(3):604-618. doi: 10.1016/j.cell.2019.08.055. Epub 2019 Oct 10.


DNA-RNA hybrids play a physiological role in cellular processes, but often, they represent non-scheduled co-transcriptional structures with a negative impact on transcription, replication and DNA repair. Accumulating evidence suggests that they constitute a source of replication stress, DNA breaks and genome instability. Reciprocally, DNA breaks facilitate DNA-RNA hybrid formation by releasing the double helix torsional conformation. Cells avoid DNA-RNA accumulation by either preventing or removing hybrids directly or by DNA repair-coupled mechanisms. Given the R-loop impact on chromatin and genome organization and its potential relation with genetic diseases, we review R-loop homeostasis as well as their physiological and pathological roles.

Publication types

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

MeSH terms

  • Chromatin / chemistry
  • Chromatin / genetics
  • DNA / chemistry
  • DNA / genetics*
  • DNA Breaks
  • DNA Repair / genetics
  • DNA Replication / genetics
  • Genomic Instability / genetics
  • Homeostasis / genetics
  • Humans
  • Nucleic Acid Conformation*
  • R-Loop Structures / genetics*
  • RNA / chemistry
  • RNA / genetics*
  • Transcription, Genetic


  • Chromatin
  • RNA
  • DNA