PerspectiveCanonical DNA Repair Pathways Influence R-Loop-Driven Genome Instability

•R-loops are an important source of DNA damage and genome instability.•DNA repair proteins implicated in tumor suppression limit R-loop-induced DNA damage.•DNA replication fork protection may exert an anti-R-loop effect.

DNA repair defects create cancer predisposition in humans by fostering a higher rate of mutations. While DNA repair is quite well characterized, recent studies have identified previously unrecognized relationships between DNA repair and R-loop-mediated genome instability. R-loops are three-stranded nucleic acid structures in which RNA binds to genomic DNA to displace a loop of single-stranded DNA. Mutations in homologous recombination, nucleotide excision repair, crosslink repair, and DNA damage checkpoints have all now been linked to formation and function of transcription-coupled R-loops. This perspective will summarize recent literature linking DNA repair to R-loop-mediated genomic instability and discuss how R-loops may contribute to mutagenesis in DNA-repair-deficient cancers.

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