Figure 6

Analysis of magnitude and reproducibility of PARPi-induced DDR readouts in CyclinA2+ vs CyclinA2- cells. (A). DDR wild type or mutant EBV cell lines (ATRp-/-, BRCA2-/-, BRCA1+/-, BRCA1+/+ genotypes, Cell Line panel 2, Materials and methods) were treated with PARP inhibitor AZD2281 (AZD, 6 μg/mL) or the combination of AZD2281 + temozolomide (AZD + TMZ, 6 μg/mL + 2 μg/mL, respectively) (columns) for 48 hr and assayed for activation of DDR readouts. Shown are Log₂Fold values measuring the magnitude of modulation of p-H2AX, p-RPA2, p-DNA-PKcs (left) or p21, p-ATM, p-BRCA1 (right) in both CyclinA2- and CyclinA2+ subsets (top). Tabulated below are the average Log₂Fold (L2F) values for each readout and treatment condition in CyclinA2- and CyclinA2+ subsets, with the paired t-test p-value comparing CyclinA2- and CyclinA2+ L2F values. Data shown are the average of two experiments (B). Shown are Coefficient of Variation (CV) values measuring the reproducibility between the two experiments shown in (A). CVs were computed for CyclinA2- and CyclinA2+ populations for each readout and treatment condition. Tabulated below are the average CVs for each readout and treatment condition in CyclinA2- and CyclinA2+ subsets and the paired t-test p-value comparing CyclinA2- and CyclinA2+ CVs.