Role for RNA:DNA hybrids in origin-independent replication priming in a eukaryotic system.

ABSTRACT: 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.

SUBMITTER: Stuckey R 

PROVIDER: S-EPMC4426422 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature