Break-induced RNA–DNA hybrids (BIRDHs) in homologous recombination: friend or foe?

Description

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.

Abstract

Ministerio de Ciencia e Innovación PID2019-104270GB-I00/BMC

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