Impaired Processing of DNA

Reduced DNA repair has been linked to an increased risk of cutaneous malignant melanoma, but insights into the molecular mechanisms of that link are scarce. The INK4a/ARF (CDKN2a) locus, which codes for the p16 and p19 proteins, is often mutated in sporadic and familial malignant melanoma, but it has not been directly associated with reduced DNA repair. We transfected unirradiated mouse fibroblast cells with UV-treated DNA to measure DNA repair in normal, p16 mutant, p19 mutant, or double mutant mouse host cells. Loss of either p16 or p19 reduced the ability of the cells to process UVinduced DNA damage, independent of cell cycle effects incurred by the loss. These results may further explain why INK4a/ARF mutations predispose to malignant melanoma, a UVinduced tumor. [J Natl Cancer Inst 2004;96:1790–93]