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

Eva Petermann, Li Lan, Lee Zou

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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.
Original languageEnglish
Pages (from-to)521-540
Number of pages20
JournalNature Reviews. Molecular Cell Biology
Issue number8
Early online date22 Apr 2022
Publication statusPublished - Aug 2022

Bibliographical note

Funding Information:
We apologize to those authors whose work could not be cited due to space constrains. E.P. is supported by Cancer Research UK (C25526/A28275) and Medical Research Council (MR/S021310/1). L.L. is supported by the NIH (GM118833). L.Z. is the James & Patricia Poitras Endow Chair for Cancer Research and support by the NIH (CA263934).

Publisher Copyright:
© 2022, Springer Nature Limited.


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