Most solar radiation-induced skin cancers arise in keratinocytes. However, the knowledge of the mechanisms of UVB damage and repair is mainly derived from studies in fibroblasts. D'Errico et al. provide evidence that there is a significant diversity in the biological response to UVB of keratinocytes and fibroblasts. They show that upon UVB irradiation, fibroblasts defective in transcription-coupled repair undergo massive apoptosis that is reduced by mdm2 overexpression (immunofluorescence). In keratinocytes, unlike fibroblasts, transcription-blocking lesions do not represent the main signal for p53 induction and apoptosis. In this cell type, the presence of an efficient global genome repair is likely to prevent the accumulation of UV photoproducts in actively transcribed genes. These findings have important implications for the mechanism of skin cancer protection after UVB damage and provide a clue for the lack of skin cancer in Cockayne syndrome. The role of cell type in the response to DNA damage should present a significant challenge for future research in the field. For details, see the article by D'Errico et al. on page 432 of this issue.