FIG. 1.

Mdm2 overexpression induces chromosome/chromatid breaks. NIH 3T3 cells (A), p53^−/− MEFs (B), or Nbs1^ΔB/ΔB MEFs (C) were left uninfected (uninf) or infected with an empty bicistronic GFP-encoding retrovirus (vector [Vec]) or a retrovirus encoding GFP and wild-type Mdm2 (Mdm2). Metaphases were examined for chromosome or chromatid breaks (see Table 1 for more details). In panels A and B, the total numbers of metaphases evaluated are indicated in each bar. Significant differences by Fisher's exact test are indicated (*, P = 0.00004; **, P = 0.00006). (C) At least 300 metaphase cells were evaluated for each bar, and the passage numbers of the MEFs are indicated. Representative Western blots for Mdm2 and β-actin are shown. (D to G) Photographs of representative examples of metaphase NIH 3T3 cells (D), p53^−/− MEFs (E and F), and Nbs1^ΔB/ΔB MEFs (G) overexpressing Mdm2. Chromatid breaks are shown in panels D, F, and G. A chromosome break is shown in panel E. Magnified views of the breaks are displayed in boxes at the corners. Nine normal chromosomes were cropped out of panel G. Arrows point to a detached centromere (D) and a chromosome fragment (F).