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R-loops as Janus-faced modulators of DNA repair

Abstract

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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Fig. 1: Current models for RNA–DNA hybrid accumulation in cis to DSBs.
Fig. 2: A function of R-loops in local transcriptional repression.
Fig. 3: Function of R-loops in the successive DSB repair steps.

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Acknowledgements

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.

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Correspondence to Gaëlle Legube.

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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

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