Crowner, AnaiyaSmith, KeelyDeSmet, Marsha2024-11-112024-11-112024-10-02Crowner A, Smith K, DeSmet M. Regulation of R-Loops in DNA Tumor Viruses. Pathogens. 2024;13(10):863. Published 2024 Oct 2. doi:10.3390/pathogens13100863https://hdl.handle.net/1805/44481R-loops are triple-stranded nucleic acid structures that occur when newly synthesized single-stranded RNA anneals to duplex DNA upon the collision of replication forks with transcription complexes. These RNA-DNA hybrids facilitate several transcriptional processes in the cell and have been described extensively in the literature. Recently, evidence has emerged that R-loops are key regulators of DNA tumor virus transcription and the replication of their lifecycle. Studies have demonstrated that R-loops on the Human Papillomavirus (HPV) genome must be resolved to maintain genome maintenance and avoid viral integration, a hallmark of HPV cancers. For Epstein-Barr virus (EBV), R-loops are formed at the oriLyt to establish lytic replication. Structural maintenance of chromosome proteins 5/6 (SMC5/6) bind to these viral R-loops to repress EBV lytic replication. Most viruses in the herpesvirales order, such as KSHV, contain R-loop-forming sequences. In this perspective, we will describe the current, although limited, literature demonstrating the importance of RNA-DNA hybrids to regulate DNA virus transcription. We will also detail potential new areas of R-loop research and how these viruses can be used as tools to study the growing field of R-loops.en-USAttribution 4.0 InternationalDNA tumor virusesR-loopsSETXReplicationTranscriptionOncogenesisArticle