Fas ligand: A sensor for DNA damage critical in skin cancer etiology

DNA-damaged cells can either repair the DNA or be eliminated through a home ostatic control mechanism termed "cellular proofreading." Elimination of DN A-damaged cells after ultraviolet radiation (UVR) through sunburn cell (apo ptotic keratinocyte) formation is thought to be pivotal for the removal of precancerous skin cells. Sunburn cell formation was found to be dependent o n Fas ligand (FasL), a pro-apoptotic protein induced by DNA damage. Chronic exposure to UVR caused 14 of 20 (70 percent) FasL-deficient mice and 1 of 20 (5 percent) wild-type mice to accumulate p53 mutations in the epidermis, Thus, Fast-mediated apoptosis is important for skin homeostasis, suggestin g that the dysregulation of Fas-FasL interactions may be central to the dev elopment of skin cancer.