A P53-DEPENDENT MOUSE SPINDLE CHECKPOINT

Cell cycle checkpoints enhance genetic fidelity by causing arrest at s pecific stages of the cell cycle when previous events have not been co mpleted. The tumor suppressor p53 has been implicated in a G(1) checkp oint. To investigate whether p53 also participates in a mitotic checkp oint, cultured fibroblasts from p53-deficient mouse embryos were expos ed to spindle inhibitors. The fibroblasts underwent multiple rounds of DNA synthesis without completing chromosome segregation, thus forming tetraploid acid octaploid cells. Deficiency of p53 was also associate d with the development of tetraploidy in vivo. These results suggest t hat murine p53 is a component of a spindle checkpoint that ensures the maintenance of diploidy.