Journal
EMBO REPORTS
Volume -, Issue -, Pages -Publisher
WILEY
DOI: 10.15252/embr.202357801
Keywords
DNA damage; DNA-RNA hybrids; DSBs; recombination; repair
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Double-strand breaks (DSBs) are highly harmful DNA damages that have significant effects on cell proliferation and genome integrity. Recent studies have shown that DSBs can enhance the formation of DNA-RNA hybrids, called break-induced RNA-DNA hybrids (BIRDHs). The source and impact of BIRDHs are still unresolved questions.
Double-strand breaks (DSBs) are the most harmful DNA lesions, with a strong impact on cell proliferation and genome integrity. Depending on cell cycle stage, DSBs are preferentially repaired by non-homologous end joining or homologous recombination (HR). In recent years, numerous reports have revealed that DSBs enhance DNA-RNA hybrid formation around the break site. We call these hybrids break-induced RNA-DNA hybrids (BIRDHs) to differentiate them from sporadic R-loops consisting of DNA-RNA hybrids and a displaced single-strand DNA occurring co-transcriptionally in intact DNA. Here, we review and discuss the most relevant data about BIRDHs, with a focus on two main questions raised: (i) whether BIRDHs form by de novo transcription after a DSB or by a pre-existing nascent RNA in DNA regions undergoing transcription and (ii) whether they have a positive role in HR or are just obstacles to HR accidentally generated as an intrinsic risk of transcription. We aim to provide a comprehensive view of the exciting and yet unresolved questions about the source and impact of BIRDHs in the cell.
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