XPA

Abstract

Xeroderma pigmentosum complementation group A (XPA) functions in initial step of the nucleotide excision repair cascade, recognition of the DNA damage, certainly within the global genome repair subpathway, and probably in the transcription-coupled repair subpathway. This chapter presents a study in which XPA–/– mice developed normally, were healthy, and fertile. Between the ages of 15 and 20 months, 15% of the mutant mice developed benign hepatocellular adenomas. The internal organs, including the GNS, showed no gross morphological abnormalities. At the age of 18 months, there were no indications of neurological degeneration. In all assays, XPA+/– mice and cells from these mice were indistinguishable from the wild type. The absence of a functional Xpa gene had consequences both in vitro and in vivo. In vitro, the residual DNA repair in XPA–/– embryonic fibroblasts as measured by UV-induced unscheduled DNA synthesis was less than five per cent of that in fibroblasts from wild-type littermates. In vivo, a low daily dose of UV-B induced hyperkeratosis and erythema followed by a high incidence of skin tumors. The type of skin tumor depended on the genetic background: squamous cell carcinomas (SCCs) occur in the XPA–/– F2 C57BL/6 × 129 mice, while SCCs and papillomas occur in XPA–/–hairless (hr) mice. The results of this study show that the XPA–/– mice mimic XP-A patients very accurately.