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How Disruption of Cell Cycle Regulators Might Predispose to Sun-Induced Skin Cancer
Thomas M. Rünger, Irene Vergilis, Papri Sarkar, Ronald A. DePinho and Norman E. Sharpless
volume 4 | issue 5
may 2005Pages: 643-645
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The Ink4a/Arf ( CDKN2a) locus encodes two proteins that regulate distinct important tumor suppressor pathways represented by p53 and Rb. Loss of either p16INK4a or p19ARF was recently reported to reduce the ability of mouse cells to repair UV-induced DNA damage and to induce a UV-mutator phenotype. This observation was independent of cell cycle effects incurred by either p16INK4a and/or p19ARF loss, as it was demonstrable in unirradiated cells using UV-treated DNA. We suggest that this might explain why germ line mutations of INK4a/ARF>/i> predispose mainly to malignant melanoma, a UV-induced skin cancer, and provides a molecular explanation for the link between melanoma-genesis and impaired DNA repair. It also further demonstrates that regulation of cell cycle check points and DNA repair in response to genomic insults, such as ultraviolet irradiation are intricately interwoven processes. Differences in the apoptotic response to ultraviolet light between melanocytes and keratinocytes might explain why INK4a/ARF mutations predispose to malignant melanoma, but not to keratinocyte-derived skin cancers.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.