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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-? 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

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

Stuckey Ruth R García-Rodríguez Néstor N Aguilera Andrés A Wellinger Ralf Erik RE

Proceedings of the National Academy of Sciences of the United States of America 20150420 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) th ...[more]

PMID: 25902524

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