Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Institute of Cancer Sciences, University of Glasgow, Glasgow, G61 1QH, UK.
Cell Death Dis. 2020 Apr 24;11(4):280. doi: 10.1038/s41419-020-2464-6.
The recent discovery of DNA:RNA hybrids, or R-loops, actively forming at DNA double-strand breaks (DSBs) has unlocked fresh insight into how RNA participates in DNA repair. However, the manner of DSB-induced R-loop formation is vital in determining its mechanism of action and is currently under debate. Here, we analyse published DNA:RNA-hybrid sequencing to elucidate the features that determine DSB-induced R-loop formation. We found that pre-existing transcriptional activity was critical for R-loop generation at break sites, suggesting that these RNAs are transcribed prior to break induction. In addition, this appeared to be a specific DSB response at the break, distinct from traditional, co-transcriptionally formed R-loops. We hypothesise that R-loop formation is orchestrated by the damage response at transcriptionally active DSB loci to specifically maintain these genomic regions. Further investigation is required to fully understand how canonical repair processes regulate R-loops at breaks and how they participate in the repair process.
最近在 DNA 双链断裂 (DSB) 处发现了 DNA:RNA 杂交体或 R 环的活性形成，这为 RNA 如何参与 DNA 修复提供了新的见解。然而，DSB 诱导的 R 环形成的方式对于确定其作用机制至关重要，目前仍存在争议。在这里，我们分析了已发表的 DNA:RNA 杂交测序，以阐明决定 DSB 诱导 R 环形成的特征。我们发现，转录活性是断裂部位产生 R 环的关键，这表明这些 RNA 是在断裂诱导之前转录的。此外，这似乎是断裂处特有的 DSB 反应，与传统的共转录形成的 R 环不同。我们假设 R 环的形成是由转录活跃的 DSB 部位的损伤反应协调的，以专门维持这些基因组区域。需要进一步研究才能充分了解规范修复过程如何在断裂处调节 R 环以及它们如何参与修复过程。
