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R-LOOPS

SWI/SNF complexes as determinants of R-loop metabolism

Nature Genetics volume 53, pages 940–941 (2021)Cite this article

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R-loops—nucleic acid structures composed of an RNA:DNA hybrid and displaced single-stranded DNA—are abundant in the genome and may impair progression of the replication fork, thus leading to accumulation of DNA damage and genome instability. A new study demonstrates that SWI/SNF chromatin-remodeling complexes are instrumental in resolving such R-loop-mediated transcription–replication conflicts, highlighting the importance of these chromatin remodelers in R-loop homeostasis and the maintenance of genome integrity.

R-loops are three-stranded nucleic acid structures consisting of an RNA:DNA hybrid and unpaired single-stranded DNA. They are involved in the regulation of several essential biological processes, including DNA repair and immunoglobulin class-switch recombination, and are a critical source of genomic instability in eukaryotic cells1,2. A growing body of experimental evidence suggests that co-transcriptionally formed R-loops may impede progression of the replication fork, thus resulting in its stalling and the accumulation of DNA breaks3. Such R-loop-mediated transcription–replication conflicts lead to increased genetic instability that may ultimately, among other consequences, contribute to the pathogenesis of neurodegenerative disorders or cancer transformation1,3, and therefore must be suppressed by the cell. In this issue, Bayona-Feliu et al. show that switch/sucrose non-fermentable (SWI/SNF) chromatin-remodeling complexes are involved in resolving the R-loop-mediated transcription–replication conflicts in immortalized cell lines derived from human cancers4.

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Fig. 1: Potential modes of SWI/SNF involvement in R-loop resolution.

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Authors and Affiliations

  1. Epigenetic Programme, Babraham Institute, Cambridge, UK

    Abdulkadir Abakir

  2. School of Medicine, University of Nottingham, Nottingham, UK

    Alexey Ruzov

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  1. Abdulkadir Abakir
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  2. Alexey Ruzov
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Correspondence to Alexey Ruzov.

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The authors declare no competing interests.

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Abakir, A., Ruzov, A. SWI/SNF complexes as determinants of R-loop metabolism. Nat Genet 53, 940–941 (2021). https://doi.org/10.1038/s41588-021-00884-1

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