1. Normal cell cycle DNA replication Doughter cells G2 phase Nuclear division Cytokinesis 1x

2. DNA damage STOP activation of p53 Checkpoint arrest DNA damage checkpoint

3. DNA repair, expression of Wip1, inactivation of p53 DNA damage START activation of p53 Recovery from the checkpoint after DNA repair

4. DNA damage Abnormally high level of Wip1 inactivation of p53 deficient checkpoint Genome instability Accumulation of mutations Cancer Transmission of Mutations to progeny Role of Wip1 oncogene in tumourigenesis 100x