Fig. 6. Toxic PARP1 activity during BER disrupts global histone monoubiquitination.
a, Representative images (left) and levels (right) of H2BmUB in WT and XRCC1−/− RPE-1 cells following mock treatment or at the indicated times after treatment with 250 μM H2O2 for 5 min. b, Representative images (left) and levels (right) of H2AmUb in WT and XRCC1−/− RPE-1 cells following mock treatment or at the indicated times after treatment with 250 μM H2O2 for 5 min. a,b, The cells were incubated with DMSO vehicle or 10 μM PARPi for 1 h before, during and following H2O2 treatment as indicated. c, Representative images (left) and levels (right) of H2BmUB in WT and XRCC1−/− RPE-1 cells following mock treatment or at the indicated times after treatment with 0.1 mg ml−1 MMS (continuous treatment). d, Representative images (left) and levels (right) of H2AmUb in WT and XRCC1−/− RPE-1 cells following mock treatment or at the indicated times after treatment with 0.1 mg ml−1 MMS (continuous treatment). c,d, The cells were incubated with DMSO vehicle or 10 μM PARPi during the MMS treatment. a–d, Data are the mean ± s.e.m. of five (a), three (b,d) and four (c) independent experiments. Statistical significance was determined using a two-way ANOVA with Tukey’s multiple comparisons test (significantly different P values are indicated). Scale bars, 10 μm.