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Intertwining roles of R-loops and G-quadruplexes in DNA repair, transcription and genome organization

Abstract

R-loops are three-stranded nucleic acid structures that are abundant and widespread across the genome and that have important physiological roles in many nuclear processes. Their accumulation is observed in cancers and neurodegenerative disorders. Recent studies have implicated a function for R-loops and G-quadruplex (G4) structures, which can form on the displaced single strand of R-loops, in three-dimensional genome organization in both physiological and pathological contexts. Here we discuss the interconnected functions of DNA:RNA hybrids and G4s within R-loops, their impact on DNA repair and gene regulatory networks, and their emerging roles in genome organization during development and disease.

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Fig. 1: Formation and resolution of R-loops.
Fig. 2: R-loops as scaffolds for RNA-dependent and error-free homologous recombination repair pathways.
Fig. 3: Diverse roles of R-loops in gene regulation.
Fig. 4: R-loop-mediated regulation of 3D genome organization.

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Acknowledgements

This work was supported by funding from the National Institutes of Health (R01NS127828 and R01GM143229 to K.S. and F32GM143832 to P.W.). We apologize to colleagues whose work could not be cited due to space limitations.

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Wulfridge, P., Sarma, K. Intertwining roles of R-loops and G-quadruplexes in DNA repair, transcription and genome organization. Nat Cell Biol 26, 1025–1036 (2024). https://doi.org/10.1038/s41556-024-01437-4

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