[DNA repair defect in xeroderma pigmentosum]

Xeroderma pigmentosum (XP) is an autosomal recessive human disease, clinically characterized by the early onset of severe photosensitivity of exposed skin to sunlight, a very high incidence of skin cancers and frequent neurological abnormalities. Cells from XP patients are hypersensitive to killing by UV-light, because they have a defect in repair of UV-light induced DNA damage. Genetic complementation analysis by cell fusion has led to the identification of at least ten genetic complementation groups, designated as group A through I, and a variant. However, the genetic basis of the physiological defect of XP has not yet been characterized. For isolation of the gene responsible for XP complementation group A, the pSV2gpt and genomic DNA from a mouse embryo were co-transfected into XP2OSSV group A XP cells. Two primary UV-resistant XP transfectants were isolated from about 1.6 X 10(5) pSV2gpt transformed XP colonies. The pSV2gpt and genomic DNA from the primary transfectants were again co-transfected into XP2OSSV cells, and a secondary UV-resistant XP transfectant was obtained by screening about 4.8 X 10(5) pSV2gpt transformed XP colonies. The secondary transfectant retained fewer mouse repetitive sequences. A mouse gene that complements the defect of XP2OSSV cells was cloned into EMBL3 vectors from the secondary transfectant. Transfections of the cloned DNA also conferred UV-resistance on another group A XP cell line, but not on group C, D, F or G XP cell lines, suggesting that the cloned DNA repair gene is specific for group A XP and may be the mouse counterpart of the group A XP human gene.