Expression and Functional Analyses of the Dxpa Gene, the Drosophila Homolog of the Human Excision Repair Gene XPA

Abstract

Xeroderma pigmentosum (XP) is a human hereditary disease characterized by a defect in DNA repair after exposure to ultraviolet light. Among the seven groups of XP, group A (XP-A) patients show the most severe deficiency in excision repair and a wide variety of cutaneous and neurological disorders. We have cloned homologs of the human XPA gene from chicken, Xenopus, and Drosophila, and sequence analysis revealed that these genes are highly conserved throughout evolution. Here, we report characterization of the Drosophila homolog of the human XPA gene (Dxpa). The Dxpa gene product shows DNA repair activities in an in vitro repair system, and Dxpa cDNA has been shown to complement a mutant allele of human XP-A cells by transfection. Polytene chromosome in situ hybridization mapped Dxpa to 3F6-8 on the X chromosome, where no mutant defective in excision repair was reported. Northern blot analysis showed that the gene is continuously expressed in all stages of fly development. Interestingly, the Dxpa protein is strongly expressed in the central nervous system and muscles as revealed by immunohistochemical analysis using anti-Dxpa antibodies, consistent with the results obtained in transgenic flies expressing a Dxpa-beta-galactosidase fusion gene driven by the Dxpa promoter.