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Review
. 2022 Aug;23(8):521-540.
doi: 10.1038/s41580-022-00474-x. Epub 2022 Apr 22.

Sources, resolution and physiological relevance of R-loops and RNA-DNA hybrids

Eva Petermann  1   2 , Li Lan  3   4 , Lee Zou  5   6
Affiliations
Review

Sources, resolution and physiological relevance of R-loops and RNA-DNA hybrids

Eva Petermann et al. Nat Rev Mol Cell Biol. 2022 Aug.

Erratum in

Abstract

RNA-DNA hybrids are generated during transcription, DNA replication and DNA repair and are crucial intermediates in these processes. When RNA-DNA hybrids are stably formed in double-stranded DNA, they displace one of the DNA strands and give rise to a three-stranded structure called an R-loop. R-loops are widespread in the genome and are enriched at active genes. R-loops have important roles in regulating gene expression and chromatin structure, but they also pose a threat to genomic stability, especially during DNA replication. To keep the genome stable, cells have evolved a slew of mechanisms to prevent aberrant R-loop accumulation. Although R-loops can cause DNA damage, they are also induced by DNA damage and act as key intermediates in DNA repair such as in transcription-coupled repair and RNA-templated DNA break repair. When the regulation of R-loops goes awry, pathological R-loops accumulate, which contributes to diseases such as neurodegeneration and cancer. In this Review, we discuss the current understanding of the sources of R-loops and RNA-DNA hybrids, mechanisms that suppress and resolve these structures, the impact of these structures on DNA repair and genome stability, and opportunities to therapeutically target pathological R-loops.

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References

    1. Crossley, M. P., Bocek, M. & Cimprich, K. A. R-loops as cellular regulators and genomic threats. Mol. Cell 73, 398–411 (2019). - PubMed - PMC - DOI
    1. Garcia-Muse, T. & Aguilera, A. R loops: from physiological to pathological roles. Cell 179, 604–618 (2019). - PubMed - DOI
    1. Niehrs, C. & Luke, B. Regulatory R-loops as facilitators of gene expression and genome stability. Nat. Rev. Mol. Cell Biol. 21, 167–178 (2020). - PubMed - PMC - DOI
    1. Marnef, A. & Legube, G. R-loops as Janus-faced modulators of DNA repair. Nat. Cell Biol. 23, 305–313 (2021). - PubMed - DOI
    1. Stodola, J. L. & Burgers, P. M. Mechanism of lagging-strand DNA replication in eukaryotes. Adv. Exp. Med. Biol. 1042, 117–133 (2017). - PubMed - DOI

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