Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells

AbstractSquamous cell carcinomas (SCCs) are associated with ultraviolet radiation and multiple genetic changes, but the mechanisms leading to genetic instability are unclear.SCCcell lines were compared to normal keratinocytes for sensitivity to ultraviolet radiation,DNArepair kinetics andDNArepair protein expression. Relative to normal keratinocytes, fourSCCcell lines were all variably sensitive to ultraviolet radiation and, except for theSCC25 cell line, were deficient in global repair of cyclobutane pyrimidine dimers, although not 6‐4 photoproducts. ImpairedDNArepair of cyclobutane pyrimidine dimers was associated with reducedmRNAexpression fromXPCbut notDDB2genes which each encode keyDNAdamage recognition proteins. However, levels ofXPCorDDB2 proteins or both were variably reduced in repair‐deficientSCCcell lines. p53 levels did not correlate withDNArepair activity or withXPCandDDB2 levels, but p63 levels were deficient in cell lines with reduced global repair. Repair‐proficientSCC25 cells depleted of p63 lostXPCexpression, early globalDNArepair activity andUVresistance. These results demonstrate that someSCCcell lines are deficient in global nucleotide excision repair and support a role for p63 as a regulator of nucleotide excision repair inSCCs.