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

Peter C. Stirling, Philip Hieter
2017 Journal of Molecular Biology  
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
more » ... 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. Graphical Abstract Background Faithful replication and segregation of DNA during cell division is essential for survival. While a low level of mutagenesis is tolerated across generations, higher mutational loads are deleterious 1 . In order to suppress the accumulation of mutations and maintain the genome, organisms have evolved a robust replication and mitotic apparatus and a semi-redundant network of DNA repair machinery and cell cycle control mechanisms. Defects in these Correspondence: pstirling@bccrc.ca, hieter@msl.ubc.ca.
doi:10.1016/j.jmb.2016.07.014 pmid:27452366 pmcid:PMC5253333 fatcat:gnvlzlrzo5fzhghw4r6y4f6phi