The tumour suppressor gene p53 is mutated in half of the human cancers, and there is still extensive morbidity and mortality associated with cancers bearing p53 mutations. Given the difficulties in developing strategies for targeting wild-type or mutant p53, further understanding of its basic biology is required for successful clinical translation. Recent studies, including ours, have challenged the previously understood model of how the p53 gene is involved in tumour suppression. We found that several p53 activated target genes implicated in DNA repair have critical functions in suppressing blood cancer development. Based on this observation, we hypothesise that coordination of DNA damage repair is the most critical mechanism by which p53 suppresses tumour development. In line with this hypothesis our laboratories current research focuses on answering following questions i) how p53 controls a DNA repair– coordinated program to protect tumorigenesis; ii) how tissue specificity controls which p53-regulated DNA repair effectors are crucial for tumour suppression and iii) how we could use p53-dependent DNA repair signaling therapeutically to kill tumour cells.