The evidenced here central role of the ATM-p53 axis could explain why a non-functional DNA damage response (due to ATM pharmacological inhibition, siRNA-mediated p53 knocking-down or p53 mutation ascribed to the Li-Fraumeni syndrome) rendered human dermal fibroblasts entirely defenseless towards UVB radiation, leading to a complete loss of cell viability. This evidence concerns the gene TP53 and Li-Fraumeni syndrome.