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Science 6 August 1999:
Vol. 285. no. 5429, pp. 898 - 900
DOI: 10.1126/science.285.5429.898
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Reports

Fas Ligand: A Sensor for DNA Damage Critical in Skin Cancer Etiology

Laurie L. Hill, Allal Ouhtit, Susan M. Loughlin, Margaret L. Kripke, Honnavara N. Ananthaswamy, Laurie B. Owen-Schaub *

DNA-damaged cells can either repair the DNA or be eliminated through a homeostatic control mechanism termed "cellular proofreading." Elimination of DNA-damaged cells after ultraviolet radiation (UVR) through sunburn cell (apoptotic keratinocyte) formation is thought to be pivotal for the removal of precancerous skin cells. Sunburn cell formation was found to be dependent on 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, FasL-mediated apoptosis is important for skin homeostasis, suggesting that the dysregulation of Fas-FasL interactions may be central to the development of skin cancer.

Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
*   To whom correspondence should be addressed. E-mail: lowensch{at}mdanderson.org

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Science. ISSN 0036-8075 (print), 1095-9203 (online)