There is a highly complex network of molecular interactions responsible for maintaining the integrity of the genome within the cell. At the center of this network is the tumor suppressor protein, p53. These data demonstrate that p53 protects normal, healthy cells from DNA damage. More importantly, the results show that p53-mediated protection from DNA damaging agents can be enhanced. We treated normal, healthy cells with selenomethionine prior to challenge with cisplatin and found that the selenium supplementation enhanced DNA repair and improved cell survival following chemotherapy. However, cells that lacked a functional copy of p53 remained sensitive to the cisplatin treatment and had no improvement in DNA repair. Furthermore, the results identify a downstream target of p53, namely Xpc, that contributes significantly to the protective response in mouse bone marrow. Xpc is a protein responsible for recognizing DNA damage, and the data reveal that mice lacking the xpc gene had substantially greater bone marrow toxicity than normal mice.