Figure 4.
Rev1 protects against endogenous DNA damage–induced senescence and apoptosis (see alsosupplemental Figure 5). Proliferation, replication, senescence, and apoptosis were quantified in bone marrow of all 4 genotypes. *P < .05; **P < .01; ***P < .001; ****P < .0001. Data are mean ± SEM. Reduced proliferation (Ki67 immunostaining) (A) and replication (BrdU and EdU incorporation) (B) in the bone marrow of moribund Rev1Xpc mice. WT: 3 m (n = 7-9), MB (n = 5-6). Xpc: 3 m (n = 6-8), MB (n = 6). Rev1: 3 m (n = 7), MB (n = 6). Rev1Xpc: 3 m (n = 6), MB (n = 9). Increased senescence and apoptosis in the bone marrow of Rev1Xpc mice as demonstrated by immunostaining for Dec1 (C), p16 (D), and caspase-3 (E). WT: 3 m (n = 4-8), MB (n = 5-6). Xpc: 3 m (n = 5-8), MB (n = 5-6). Rev1: 3 m (n = 3-7), MB (n = 6). Rev1Xpc: 3 m (n = 3-6), MB (n = 6-8). m, months; MB, moribund (see Figure 2A for survival data). The fraction of positive cells shown was normalized relative to 3-month-old WT bone marrow.