XPA Background Information Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a genetic predisposition to sunlight-induced skin cancer due to deficiencies in the DNA repair enzymes. The most frequent mutations are found in the XP genes of group A through G and group V, which encode nucleotide excision repair proteins. Nucleotide excision repair (NER) is the normal cellular response to DNA damage induced by UV irradiation and is disrupted in patients with XP. Xeroderma pigmentosum group A (XPA) is an essential NER factor that coordinates the collection of a preincision complex during the processing of DNA damage. XPA may also have a role in the repair of oxidized DNA bases. XPA is sensitive not only to the structure of the DNA double helix, but also to bulky groups incorporated into DNA. XPA forms a homodimer in the absence of DNA, but binds to DNA in both monomeric and dimeric forms. The dimerically bound XPA is much more efficient, so cells probably regulate XPA activity in a concentration-dependent manner. XPA deficient organisms cannot repair UV-induced DNA damage and thus acquire skin cancers by UV irradiation very easily.
