R-loops are non-B DNA structures with intriguing dual consequences for gene expression and genome stability. In addition to their recognized roles in triggering DNA double-strand breaks (DSBs), R-loops have recently been demonstrated to accumulate in cis to DSBs, especially those induced in transcriptionally active loci. In this Review, we discuss whether R-loops actively participate in DSB repair or are detrimental by-products that must be removed to avoid genome instability.
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Funding in G.L.’s laboratory was provided by grants from the European Research Council (ERC-2014-CoG 647344), the Agence Nationale pour la Recherche (ANR-14-CE10-0002-01), the Institut National Contre le Cancer (INCA) and the Ligue Nationale Contre le Cancer (LNCC). We thank S. Egloff (CBI, Toulouse) and D. Lane (CBI, Toulouse) for their critical reading of the manuscript and apologize to colleagues whose work was not cited due to space constraints.
The authors declare no competing interests.
Peer review information Nature Cell Biology thanks Nick Proudfoot, Lee Zou and the other, anonymous, reviewer for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Marnef, A., Legube, G. R-loops as Janus-faced modulators of DNA repair. Nat Cell Biol 23, 305–313 (2021). https://doi.org/10.1038/s41556-021-00663-4
Nature Reviews Molecular Cell Biology (2022)
A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrid accumulation
Nature Communications (2022)
Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells
Scientific Reports (2022)
Cellular and Molecular Life Sciences (2022)
Nature Communications (2021)