Defining R-loop classes and their contributions to genome instability

Daisy Castillo-Guzman, Frédéric Chédin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number103182
JournalDNA Repair
Volume106
DOIs
StatePublished - Oct 2021

Keywords

  • DNA damage
  • Elongation
  • Genome instability
  • Promoter-pausing
  • R-loops
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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