Sun-exposed human skin contains an extensive number of phenotypicallyintact cell compartments bearing missenseand nonsense mutations in the p53 tumor suppressor gene.

Deep sequencing of sun-exposed and shielded microdissectedskin from mid-life individuals revealed that persistent p53 mutations had accumulated in 14% of all epidermal cells, with no apparent signs of a growth advantage of the affected cell compartments.

Furthermore, 6% of the mutated epidermal cells encoded a truncated protein.The abundance of these events, not taking into account intronmutations and mutations in other genes that also may have functional implications, suggests an extensive tolerance of human cells to severe genetic alterations caused by ultraviolet light, with an estimated annual rate of accumulation of approximately 35,000 new persistent protein altering p53 mutations in sun exposed skin of a human individual.