Stuckey, RuthGarcía Rodriguez, NéstorAguilera López, AndrésWellinger, Ralf Erik2015-10-012015-10-0120151091-64900027-8424http://hdl.handle.net/11441/29075DNA replication initiates at defined replication origins along eukaryotic chromosomes, ensuring complete genome duplication within a single S-phase. A key feature of replication origins is their ability to control the onset of DNA synthesis mediated by DNA polymerase-α and its intrinsic RNA primase activity. Here, we describe a novel origin-independent replication process that is mediated by transcription. RNA polymerase I transcription constraints lead to persistent RNA:DNA hybrids (R-loops) that prime replication in the ribosomal DNA locus. Our results suggest that eukaryotic genomes have developed tools to prevent R-loop–mediated replication events that potentially contribute to copy number variation, particularly relevant to carcinogenesis.application/pdfengAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/RNA:DNA hybridsRNase Htopoisomerase 1replicationribosomal DNARole for RNA: DNA hybrids in origin-independent replication priming in a eukaryotic systeminfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.1073/pnas.1501769112