The Skin and Ultraviolet Radiation: Effects on DNA and Carcinogenesis

The hereditary syndromes xeroderma pigmentosum (XP) and Cockayne syndrome (CS) have mutations in the nucleotide excision repair (NER) pathway. XP shows an extremely high incidence of solar-induced skin cancer and in some cases neurological disease. CS shows photosensitivity, developmental disorders and neurological disease, but not cancer. XP is associated with mutations in components of the global genome repair (GGR) branch of NER that repairs regions of the genome that do not code for proteins and the non-transcribed strands of expressed protein-coding genes. CS is associated with mutations in components of the transcription coupled repair (TCR) pathway that repair the transcribed strand of protein-expressing genes. Studies of mutagenesis from UV light in XP and CS cells, and squamous cell carcinomas from XP patients, show that defective GGR predisposes to high mutation frequencies and solar-induced skin cancer, despite efficient TCR which does not protect XP patients; defects in TCR, however, only increases cell killing from UV light, but reportedly does not increase mutations in transcribed human chromosomal genes.