Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, Seville, Spain.
EMBO Rep. 2023 Dec 6;24(12):e57801. doi: 10.15252/embr.202357801. Epub 2023 Oct 11.
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.
双链断裂（DSBs）是最具危害性的 DNA 损伤，对细胞增殖和基因组完整性有重大影响。根据细胞周期阶段的不同，DSBs 可优先通过非同源末端连接或同源重组（HR）进行修复。近年来，大量报告揭示了 DSB 会增强断裂位点周围 DNA-RNA 杂交的形成。我们将这些杂交体称为“断裂诱导的 RNA-DNA 杂交体（BIRDHs）”，以将其与由 DNA-RNA 杂交体和转录过程中发生的单链 DNA 位移组成的零星 R 环区分开来。在这里，我们综述并讨论了关于 BIRDHs 的最相关数据，重点关注两个主要问题：（i）DSB 后是否通过新转录形成 BIRDHs，还是通过正在转录的 DNA 区域中预先存在的新生 RNA 形成；（ii）它们在 HR 中是否具有积极作用，还是仅仅是转录固有风险意外产生的 HR 障碍。我们旨在提供对 BIRDHs 在细胞中的来源和影响的令人兴奋但尚未解决的问题的全面了解。
