TY - JOUR TI - RNase H enables efficient repair of R-loop induced DNA damage AU - Amon, Jeremy D AU - Koshland, Douglas A2 - Aguilera, Andrés VL - 5 PY - 2016 DA - 2016/12/10 SP - e20533 C1 - eLife 2016;5:e20533 DO - 10.7554/eLife.20533 UR - https://doi.org/10.7554/eLife.20533 AB - 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 in Saccharomyces 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. KW - R-loops KW - RNase H KW - genome instability KW - break-induced replication KW - rDNA KW - DNA repair JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -