p53 inhibits entry into mitosis when DNA synthesis is blocked

Human and mouse fibroblasts with normal p53 fail to enter mitosis when DNA synthesis is blocked by aphidicolin or hydroxyurea, Isogenic p53-null fibro blasts do enter mitosis with incompletely replicated DNA, revealing that p5 3 contributes to a checkpoint that ensures that mitosis does not occur unti l DNA synthesis is complete, When treated with N-(phosphonacetyl)-L-asparta te (PALA), which inhibits pyrimidine nucleotide synthesis, leading to synth esis of damaged DNA from highly unbalanced dNTP pools, p53-null cells enter mitosis after they have completed DNA replication, but cells with wild-typ e p53 do not, revealing that p53 also mediates a checkpoint that monitors t he quality of newly replicated DNA.