EXPRESSION AND FUNCTIONAL ANALYSES OF THE DXPA GENE, THE DROSOPHILA HOMOLOG OF THE HUMAN EXCISION-REPAIR GENE XPA

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 d eficiency in excision repair and a wide variety of cutaneous and neuro logical 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 (Dxp a). The Dxpa gene product shows DNA repair activities in an in vitro r epair system, and Dxpa cDNA has been shown to complement a mutant alle le of human XP-A cells by transfection. Polytene chromosome in situ hy bridization mapped Dxpa to 3F6-8 on the X chromosome, where no mutant defective in excision repair was reported. Northern blot analysis show ed that the gene is continuously expressed in all stages of fly develo pment. Interestingly, the Dxpa protein is strongly expressed in the ce ntral nervous system and muscles as revealed by immunohistochemical an alysis using anti-Dxpa antibodies, consistent with the results obtaine d in transgenic flies expressing a Dxpa-beta-galactosidase fusion gene driven by the Dxpa promoter.