(A) MMR mutation frequencies in recurrent glioblastoma. (B) MTT viability assay in GS-5 cells; 1-way ANOVA; mean ± SEM. (C) Temozolomide (TMZ) concentration-response assay in GS-5 cells; 2-way ANOVA; mean ± SEM. (D) Postrecurrence survival (PRS) of patients with glioblastoma; Cox regression accounting for age, MGMT, and TP53 status. (E) Schematic of murine glioblastoma modeling; Scale bar: 100 μm. (F) Survival of untreated glioblastoma-bearing mice; 2-tailed log-rank. (G) BrdU incorporation in murine glioblastomas 24 hours after a single pulse (50 mg/kg); 2-tailed Wilcoxon rank-sum. (H) M:G2 ratio based on phospho-histone H3 (pHH3) staining; 2-tailed Wilcoxon rank-sum; Scale bar: 10 μm; (I) Survival of untreated glioblastoma-bearing mice; 2-tailed log-rank. (J and K) Reporter assays quantifying nonhomologous end joining (J) and homologous recombination (K) in HEK293 cells; 2-tailed t test. (L and M) Metaphase spreads in HEK293 6 hours after 2 Gy irradiation (representative images) (L) and quantification of chromosomal breaks; 2-tailed t test; Scale bar: 10 μm (M). (N, O) γ-H2ax staining of murine glioblastoma cells 8 hours after 2 Gy irradiation; Scale bar: 10 μm (N), quantification of cells in mitotic catastrophe; 2-tailed Wilcoxon rank-sum (O). (P and Q) Comet assay in GS-9 cells 3 hours after 5 Gy irradiation; Scale bar: 70 μm; 2-tailed Wilcoxon rank-sum. (R) MTT viability assay 48 hours after irradiation in GS-9 cells; 1-way ANOVA. (S–U) Survival of glioblastoma-bearing mice after mock or 5 × 2 Gy head irradiation; 2-tailed log-rank. (V) Overall survival of NOA-8 patients by treatment sequence; log-rank. RT, radiotherapy.