Recent Discoveries in the Use of R-loops to Regulate the Lifecycles of DNA Tumor Viruses

Abstract

          R-loops are triple-stranded nucleic acid structures that occur normally as a part of transcription, when single-stranded RNA anneals with duplex DNA. It has been established that R-loops are important for mammalian gene regulation and genome stability. New evidence has shown that R-loops are key contributors to the lifecycles of DNA tumor viruses (e.g. Human papillomavirus (HPV), Epstein-Barr virus (EBV), and Kaposi sarcoma-associated herpesvirus (KSHV)). DNA tumor viruses carefully maintain their genomes as episomes, balancing gene expression for viral replication while avoiding immune activation or host cell death. Recent studies have demonstrated that disruption of R-loop homeostasis can lead to replication stress, genomic instability, and increased oncogenic signaling. This review summarizes recent discoveries from the past year on DNA tumor viruses and R-loops, emphasizing their mechanistic roles in viral persistence and cancer development.