Projects per year
Abstract
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 language | English |
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Journal | Nature Reviews. Molecular Cell Biology |
Early online date | 22 Apr 2022 |
DOIs | |
Publication status | E-pub ahead of print - 22 Apr 2022 |
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Dive into the research topics of 'Sources, resolution and physiological relevance of R-loops and RNA–DNA hybrids'. Together they form a unique fingerprint.Projects
- 2 Active
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Investigating the effects of a de-regulated transcription machinery on replication stress in cancer
1/09/19 → 31/08/25
Project: Research
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Characterising novel recombination pathways at DNA adducts of the environmental mutagen BDPE
15/03/19 → 31/12/22
Project: Research Councils