Similar nucleotide excision repair capacity in melanocytes and melanoma cells.
Sunlight UV exposure produces DNA photoproducts in skin that are repaired solely by nucleotide excision repair in humans. A significant fraction of melanomas are thought to result from UV-induced DNA damage that escapes repair; however, little evidence is available about the functional capacity of normal human melanocytes, malignant melanoma cells, and metastatic melanoma cells to repair UV-induced photoproducts in DNA. In this study, we measured nucleotide excision repair in both normal melanocytes and a panel of melanoma cell lines. Our results show that in 11 of 12 melanoma cell lines tested, UV photoproduct repair occurred as efficiently as in primary melanocytes. Importantly, repair capacity was not affected by mutation in the N-RAS or B-RAF oncogenes, nor was a difference observed between a highly metastatic melanoma cell line (A375SM) or its parental line (A375P). Lastly, we found that although p53 status contributed to photoproduct removal efficiency, its role did not seem to be mediated by enhanced expression or activity of DNA binding protein DDB2. We concluded that melanoma cells retain capacity for nucleotide excision repair, the loss of which probably does not commonly contribute to melanoma progression.
Gaddameedhi
Shobhan
S
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
Kemp
Michael G
MG
Reardon
Joyce T
JT
Shields
Janiel M
JM
Smith-Roe
Stephanie L
SL
Kaufmann
William K
WK
Sancar
Aziz
A
D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D011905:Genes, ras / Q000502:physiology*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008544:Melanocytes / Q000502:physiology*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011509:Proteoglycans / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
C117669:DDB2 protein, human; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C059485:matrigel; D003094:Collagen; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf