Previous work showed that RNase H2 activity helps triple-negative breast cancer (TNBC) cells manage high levels of replication stress, offering new therapeutic insights. Researchers from The University of Texas MD Anderson Cancer Center and Cleveland Clinic now show that cells escaping senescence depend on overexpression of RNase H2, which removes misincorporated ribonucleotides from genomic DNA. They confirmed that TNBCs rely on RNase H2 to tolerate high replication stress.