Defining R-loop classes and their contributions to genome instability

DNA Repair (Amst). 2021 Oct;106:103182. doi: 10.1016/j.dnarep.2021.103182. Epub 2021 Jul 17.

Abstract

R-loops are non-B DNA structures that form during transcription when the nascent RNA anneals to the template DNA strand forming a RNA:DNA hybrid. Understanding the genomic distribution and function of R-loops is an important goal, since R-loops have been implicated in a number of adaptive and maladaptive processes under physiological and pathological conditions. Based on R-loop mapping datasets, we propose the existence of two main classes of R-loops, each associated with unique characteristics. Promoter-paused R-loops (Class I) are short R-loops that form at high frequency during promoter-proximal pausing by RNA polymerase II. Elongation-associated R-loops (Class II) are long structures that occur throughout gene bodies at modest frequencies. We further discuss the relationships between each R-loop class with instances of genome instability and suggest that increased class I R-loops, resulting from enhanced promoter-proximal pausing, represent the main culprits for R-loop mediated genome instability under pathological conditions.

Keywords: DNA damage; Elongation; Genome instability; Promoter-pausing; R-loops; Transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Eukaryota / genetics
  • Eukaryota / metabolism
  • Genomic Instability*
  • Humans
  • R-Loop Structures*
  • Transcription, Genetic*