The evolution of diverse biological responses to DNA damage: insights fromyeast and p53

The cellular response to ionizing radiation provides a conceptual framework for understanding how a yeast checkpoint system, designed to make binary d ecisions between arrest and cycling, evolved in a way as to allow reversibl e arrest, senescence or apoptosis in mammals. We propose that the diversity of responses to ionizing radiation in mammalian cells is possible because of the addition of a new regulatory control module involving the tumour-sup pressor gene p53. We review the complex mechanisms controlling p53 activity and discuss how the p53 regulatory module enables cells to grow, arrest or die by integrating DNA damage checkpoint signals with the response to norm al mitogenic signalling and the aberrant signalling engendered by oncogene activation.