Figure 5

Repositioning of chromosome territories following DNA damage requires ATM/ATR activity. ATM activity in NHDFs was inhibited by treatment with 10 μM KU55933 for 1 hour. Pre-treatment with KU55933 inhibits phosphorylation of γH2AX after DNA damage as observed by IF staining (A, B, C) and Western blot analyses (D). Chromosome 19 repositions from the nuclear interior (E, E’, E”) to the periphery after DNA damage (G, G’, G”). This repositioning is inhibited in DNA-damaged cells pre-treated with ATM/ATR activity inhibitors (H, H’, H”). Chromosome 11 remains at the nuclear periphery in cells subjected to the above treatments (E–H, E’-H’, E”-H”). In ATM mutant fibroblasts AT2BE and AT5B1, chromosome 12 occupies the nuclear periphery (I, J, K, M, N, O) while chromosome 19 remains in the nuclear interior (I, J, L, M, N, P) in both undamaged cells (black bars) as well as in cells post DNA damage treatment (gray bars). * indicates P = 0.05 as assessed by ANOVA.