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Proc Natl Acad Sci U S A. 2015 May 5;112(18):5779-84. doi: 10.1073/pnas.1501769112. Epub 2015 Apr 20.

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

Author information

1
Department of Molecular Biology, Centro Andaluz de Biología Molecular y Medicina Regenerativa-Universidad de Sevilla, 41092 Seville, Spain.
2
Department of Molecular Biology, Centro Andaluz de Biología Molecular y Medicina Regenerativa-Universidad de Sevilla, 41092 Seville, Spain ralf.wellinger@cabimer.es.

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.

KEYWORDS:

RNA:DNA hybrids; RNase H; replication; ribosomal DNA; topoisomerase 1

PMID:
25902524
PMCID:
PMC4426422
DOI:
10.1073/pnas.1501769112
[Indexed for MEDLINE]
Free PMC Article

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