The protein product of the xeroderma pigmentosum group C (XPC) gene is a DNA damage recognition factor that functions early in the process of global genomic nucleotide excision repair. Regulation of XPC expression is governed in part by p53 at the transcriptional level. To identify the regulatory elements involved in the p53-dependent control of XPC expression, we performed a quantitative PCR tiling experiment using multiple regularly spaced primer pairs over an 11-kb region centered around the XPC transcriptional start site. p53 chromatin immunoprecipitation was performed following ultraviolet irradiation, and DNA was analyzed for enrichment at each of 48 amplicons covering this region. A segment just upstream of the XPC translational initiation site was significantly enriched, whereas no enrichment of any other region was noted. In vitro promoter reporter assays and gel retardation assays were used to confirm the p53 responsiveness of this region and to define the minimal region with stimulating activity. We identified a p53 response element that has significant similarity to a consensus sequence, with 3 mismatches. This response element is unique in that part of the p53 binding site included the coding sequence for the first 2 amino acids in the XPC protein. © The Author(s) 2012.