Xeroderma Pigmentosum — A Human Model of Defective DNA Repair
The human disease xeroderma pigmentosum (XP) has been intensively studied ever since Cleaver first provided evidence of defective repair of DNA damage in 1968 (1). The disease is inherited by an autosomal recessive mode and is clinically characterized chiefly by severe photosensitivity of the skin and eyes, a high frequency of a variety of neurologic abnormalities and an almost 100% incidence of malignant skin tumors. It is noteworthy that tumors in other sites have not been reported with an abnormal frequency in this disease. All known cases of XP fall into two major classes, based on the ability of cells in culture (usually fibroblasts) to repair DNA damage caused by ultraviolet (UV) radiation. So-called typical or classical XP is characterized by defective nucleotide excision repair of pyrimidine dimers in asynchronous fibroblast cultures exposed to UV light at~254 nm. XP variant cases are clinically indistinguishable from the typical form of XP, but fail to show defects in any of the currently available biochemical parameters that directly or indirectly measure the excision of pyrimidine dimers in asynchronous fibroblast cultures. The technique of cell hybridization has been used to classify typical XP cases into a number of apparently distinct genetic groups (complementation groups) defined by their ability to complement the restoration of normal levels of excision repair measured by unscheduled DNA synthesis (UDS) in heterodikaryons. At the time of writing, approximately 100 cases have been designated in the literature by an internationally agreed upon nomenclature (2) and assigned to one of 7 complementation groups. The clinical symptoms and signs and the variety of genetic, cellular and biochemical defects associated with XP have been extensively reviewed by a number of authors (3–6) in recent years and the interested reader is referred to this literature for a more detailed description. In this article I have specifically focused on some of the literature published during the past two years and have attempted to draw attention to selected new aspects of the disease.
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