Resolution of ROS-induced G-quadruplexes and R-loops at transcriptionally active sites is dependent on BLM helicase.

R-loops and G-quadruplexes (G4s) are noncanonical secondary DNA structures. Here, we show that reactive oxygen species (ROS) induce G4 formation as well as R-loops at transcriptionally active sites. Importantly, the G4 structure is subsequently triggered by R-loop formation after damage. Once G4 is formed within an R-loop, it reversely stabilizes the R-loop. Notably, the helicase activity of Bloom syndrome protein is essential for the resolution of both R-loops and G4s. Unresolved G4s and R-loops delay the repair of ROS-induced damage at actively transcribed sites. Together, our results demonstrate that interregulation between R-loops and G4s induced by ROS is essential for repair at transcriptionally active sites.