biostudies-literatureStuckey RConsejería Economía, Innovación, Ciencia y Empleo, Junta de AndaluciaMinisterio de Ciencia e Innovación5779-84https://www.ebi.ac.uk/biostudies/studies/S-EPMC4426422biostudies-literatureUnknown112(18)DNA 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.Proceedings of the National Academy of Sciences of the United States of AmericaRole for RNA:DNA hybrids in origin-independent replication priming in a eukaryotic system.PMC4426422BIO2006-08051P09/CVI4567P08-CTS-04297BIO-026BIO-102P11-CTS-7962BFU2010-21339CSD2007-0015BFU2010-16372Garcia-Rodriguez NWellinger REAguilera AStuckey RfalseRole for RNA:DNA hybrids in origin-independent replication priming in a eukaryotic system.DNA 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.2015-01-01T00:00:00Z2015 May2025-04-04T07:30:29.565Z2019-03-27T01:51:19ZS-EPMC44264222590252410.1073/pnas.1501769112