Here, our results from mice in which p53 activity was temporarily blocked during irradiation reveal a new paradigm for the role of the p53 response to acute DNA damage in radiation-induced lymphomagenesis: in p53 WT mice, the acute DNA damage response activates p53 in the bone marrow to promote radiation-induced lymphoma in the thymus via a non-cell-autonomous mechanism (Fig. 7). The gene discussed is TP53; the disease is lymphoma.