Recently, it has been discovered that the immediate activation of p53 upon DNA damage mediates many toxic side effects, but is not required for the suppression of carcinogenesis.61 Therefore, efficient p53 activity is needed for tumor growth suppression during the period following recovery from DNA damage.42 We suggest that transient LZAP depletion or inhibition of LZAP activities toward p53 before DNA-damaging anticancer therapy could minimize p53-dependent toxicity of the treatment in normal tissues without decreasing the tumor-suppressive p53 function. The gene discussed is CDK5RAP3; the disease is neoplasm.