EWSR1 and Ewing sarcoma: In Ewing sarcoma tumors, DNA replication stress is driven by various factors, including cell-cycle dysregulation, increased frequency of R-loops, elevated levels of the helicase SLFN11, loss of the cohesin subunit STAG2, upregulation of nucleoside transporters, haploinsufficiency of the EWSR1 gene, functional loss of ATM activity, and a BRCA1-deficient phenotype (refs. 8–16; bioRxiv 2024:2023.04.30.538578).