title: Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells.
abstract: Squamous cell carcinomas (SCCs) 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 SCC25 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 DDB2 genes which each encode key DNA damage recognition proteins. However, levels of XPC or DDB2 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 DDB2 levels, but p63 levels were deficient in cell lines with reduced global repair. Repair-proficient SCC25 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 SCCs.
authors: Dermatology Research Unit, San Francisco VA Medical Center, San Francisco, CA.|Department of Dermatology, University of California at San Francisco, San Francisco, CA.
authors: Tiffany K
authors: TK
authors: Dong
authors: Dermatology Research Unit, San Francisco VA Medical Center, San Francisco, CA.
authors: Katherine
authors: K
authors: Ona
authors: Dermatology Research Unit, San Francisco VA Medical Center, San Francisco, CA.
authors: Amy E
authors: AE
authors: Scandurra
authors: Dermatology Research Unit, San Francisco VA Medical Center, San Francisco, CA.|Department of Dermatology, University of California at San Francisco, San Francisco, CA.
authors: Stephanie K
authors: SK
authors: Demetriou
authors: Dermatology Research Unit, San Francisco VA Medical Center, San Francisco, CA. ohd@derm.ucsf.edu.|Department of Dermatology, University of California at San Francisco, San Francisco, CA. ohd@derm.ucsf.edu.
authors: Dennis H
authors: DH
authors: Oh
mesh_terms: D001681:Biological Assay; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004260:DNA Repair; D042822:Genomic Instability; D006801:Humans; D015603:Keratinocytes / Q000473:pathology / Q000528:radiation effects; D000073658:Loss of Function Mutation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014466:Ultraviolet Rays
chemical_list: C081876:CKAP4 protein, human; D008565:Membrane Proteins