Fig. 6

Relative abundances between APLF and c-NHEJ factors in response to E2F1 determine patient survival. a OS of BC patients with high E2F1 accompanied by a ‘high APLF/high DCLRE1C’ (blue), ‘low APLF/low DCLRE1C’ (red), ‘high APLF/low DCLRE1C’ (purple) or ‘low APLF/high DCLRE1C’ (green) tumor signature. Patients with high expression of either APLF (‘high APLF/low DCLRE1C’, purple) or DCLRE1C (‘low APLF/high DCLRE1C’, green) have a longer median survival than patients whose tumors lack APLF plus DCLRE1C (red), but their survival time is shorter than with high expression of both (blue), indicating that these two c-NHEJ factors exert a combinatorial effect on survival of high E2F1-expressing BC patients. b Proposed mechanism of the impact of E2F1 on c-NHEJ factors. E2F1 upregulates core factors of c-NHEJ except for APLF. During BC progression, the MIR888 promoter becomes hypomethylated, a fact that permits its ectopic activation by high levels of E2F1 and results to APLF scarcity. The disturbance in the stoichiometry between APLF and core factors of the c-NHEJ multiprotein complex reduces DSB repair and facilitates aggressiveness