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Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells
Author(s) -
Dong Tiffany K.,
Ona Katherine,
Scandurra Amy E.,
Demetriou Stephanie K.,
Oh Dennis H.
Publication year - 2016
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.12625
Subject(s) - pyrimidine dimer , nucleotide excision repair , dna repair , cell culture , dna damage , biology , dna repair protein xrcc4 , microbiology and biotechnology , dna , cancer research , chemistry , genetics
Squamous cell carcinomas ( SCC s) are associated with ultraviolet radiation and multiple genetic changes, but the mechanisms leading to genetic instability are unclear. SCC cell lines were compared to normal keratinocytes for sensitivity to ultraviolet radiation, DNA repair kinetics and DNA repair protein expression. Relative to normal keratinocytes, four SCC cell lines were all variably sensitive to ultraviolet radiation and, except for the SCC 25 cell line, were deficient in global repair of cyclobutane pyrimidine dimers, although not 6‐4 photoproducts. Impaired DNA repair of cyclobutane pyrimidine dimers was associated with reduced mRNA expression from XPC but not DDB 2 genes which each encode key DNA damage recognition proteins. However, levels of XPC or DDB 2 proteins or both were variably reduced in repair‐deficient SCC cell lines. p53 levels did not correlate with DNA repair activity or with XPC and DDB 2 levels, but p63 levels were deficient in cell lines with reduced global repair. Repair‐proficient SCC 25 cells depleted of p63 lost XPC expression, early global DNA repair activity and UV resistance. These results demonstrate that some SCC cell lines are deficient in global nucleotide excision repair and support a role for p63 as a regulator of nucleotide excision repair in SCC s.