title: Canonical DNA Repair Pathways Influence R-Loop-Driven Genome Instability.
abstract: 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.
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, V5Z1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, V6H3N1, Canada. Electronic address: pstirling@bccrc.ca.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Stirling
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, V6H3N1, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, V6T1Z4, Canada. Electronic address: hieter@msl.ubc.ca.
authors.forename: Philip
authors.initials: P
authors.lastname: Hieter
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics*; D004261:DNA Replication; D042822:Genomic Instability; D006801:Humans; D009690:Nucleic Acid Conformation; D014158:Transcription, Genetic
chemical_list: D045643:DNA Repair Enzymes
keywords: DNA repair; Fanconi Anemia; Fork protection; Genome Instability; R-loops