title: RNase H enables efficient repair of R-loop induced DNA damage.
abstract: R-loops, three-stranded structures that form when transcripts hybridize to chromosomal DNA, are potent agents of genome instability. This instability has been explained by the ability of R-loops to induce DNA damage. Here, we show that persistent R-loops also compromise DNA repair. Depleting endogenous RNase H activity impairs R-loop removal inSaccharomyces cerevisiae, causing DNA damage that occurs preferentially in the repetitive ribosomal DNA locus (rDNA). We analyzed the repair kinetics of this damage and identified mutants that modulate repair. We present a model that the persistence of R-loops at sites of DNA damage induces repair by break-induced replication (BIR). This R-loop induced BIR is particularly susceptible to the formation of lethal repair intermediates at the rDNA because of a barrier imposed by RNA polymerase I.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Jeremy D
authors.identifier: 0000-0002-8748-5228
authors.initials: JD
authors.lastname: Amon
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Douglas
authors.identifier: 0000-0003-3742-6294
authors.initials: D
authors.lastname: Koshland
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D016914:Ribonuclease H / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*
chemical_list: D016914:Ribonuclease H
keywords: DNA repair; R-loops; RNase H; S. cerevisiae; break-induced replication; chromosomes; genes; genome instability; rDNA