Open AccessImpaired Processing of DNA Photoproducts and Ultraviolet Hypermutability With Loss of p16INK4a or p19ARF
Author(s) -
Papri Sarkar-Agrawal,
Irene Vergilis,
Norman E. Sharpless,
Ronald A. DePinho,
Thomas M. Rünger
Publication year - 2004
Publication title -
journal of the national cancer institute
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.797
H-Index - 356
eISSN - 1460-2105
pISSN - 0027-8874
DOI - 10.1093/jnci/djh307
Subject(s) - cdkn2a , dna damage , melanoma , mutant , dna repair , cancer research , biology , dna , transfection , microbiology and biotechnology , genetics , cell culture , gene
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(INK4a) and p19ARF 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, p16INK4a mutant, p19ARF mutant, or double mutant mouse host cells. Loss of either p16(INK4a) or p19ARF reduced the ability of the cells to process UV-induced 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 UV-induced tumor.