Fig. 7.

STAG2 deficiency in human cancer cells creates a synthetic lethality with DNA double-strand break repair factors and increased sensitivity to ionizing radiation. a Quantitation of survival from shRNA synthetic lethality screen in STAG2 isogenic H4 glioblastoma cells (parental = STAG2 mutant, STAG2 KI = wildtype). Each data point is the mean of 8 replicates from 2 independent experiments, and error bars show standard error of the mean. b Representative phase contrast images of STAG2 isogenic H4 glioblastoma cells showing synthetic lethality of STAG2 inactivation with shRNA depletion of the non-homologous end joining factor DNA-PKcs. c Quantitation of survival from shRNA synthetic lethality screen in STAG2 isogenic RPE shTP53 cells. Each data point is the mean of 8 replicates from 2 independent experiments, and error bars show standard error of the mean. d Representative phase contrast images of STAG2 isogenic RPE shTP53 cells showing synthetic lethality of STAG2 knockout with shRNA depletion of the non-homologous end joining factor DNA-PKcs, but not the base excision repair factor DNA polymerase β. e Summary of results from shRNA synthetic lethality screen in four pairs of STAG2 isogenic human cells (H4 glioblastoma, 42MGBA glioblastoma, TC-106 Ewing sarcoma, and RPE hTERT shTP53). HR, homologous recombination. NHEJ, non-homologous end joining. BER, base excision repair. NER, nucleotide excision repair. f Survival plots of STAG2 isogenic H4 glioblastoma cells (parental = STAG2 mutant, STAG2 KI = wildtype) following gamma irradiation or ultraviolet irradiation. Each data point is the mean of 12 replicates from 3 independent experiments, and error bars show standard error of the mean. Source data are provided as a Source Data file