PRMT5 and Ewing sarcoma: We show that the expression and activity of the arginine methyltransferases PRMT1 and PRMT5 are elevated in Ewing sarcoma and that inhibition of PRMT1 or PRMT5 with pre-clinical inhibitors leads to growth arrest and apoptosis that is dependent on the expression of the driver oncogene EWSR1::FLI1. Mechanically, we show that PRMT1 and PRMT5 inhibitors promote DNA damage, and that PRMT5 inhibitors synergise with the PARP inhibitor olaparib to induce elevated DNA damage and reduced cell viability.