EWS::FLI1-DHX9 Interaction Promotes Ewing Sarcoma Sensitivity to DNA Topoisomerase 1 Poisons by Altering R-Loop Metabolism

Scientists described a novel mechanism of sensitivity to DNA topoisomerase 1 poisons in Ewing sarcoma. EWS::FLI1 prevents the resolution of R-loops induced by these drugs via sequestering DHX9 helicase, ultimately resulting in R-loop accumulation, replication stress, and genome instability.