UV-induced DNA damage, mutations and skin cancer.

Most nonmelanoma and melanoma skin cancers are linked to sun exposure. Ultraviolet B (UVB, 280 to 320 nm) radiation from the sun induces various forms of DNA damage in skin cells. A major type of damage induced by UVB is the cyclobutane pyrimidine dimer (CPD). We discuss its sequence-dependent formation in the genome, mechanisms of its repair, the mutagenic hydrolytic conversion of intra-dimer cytosine to uracil, and DNA polymerase bypass reactions operating on UV damage. Another important DNA lesion is the (6-4) photoproduct, which despite its rapid repair, may also contribute to mutagenesis. These UV lesions predominantly induce the formation of C to T transition mutations at adjacent pyrimidine sequences containing cytosine. These characteristic mutations are found in human sun-exposed skin and in skin cancer genomes decades after exposure and are a prime example of environmental mutagenesis. We also discuss the relevance of UVA radiation (320 to 400 nm) for DNA damage and sunlight-induced mutagenesis and its potential role in melanoma and other skin tumors.