Studies with a RAD14 deletion mutation indicated the absolute requirement of the gene in the DNA incision process. (1992) reported the characterization of the yeast RAD14 gene and found that it encodes a highly hydrophilic 247-residue protein containing zinc finger motifs with high similarity to the protein encoded by the human XPA gene. In the yeast Saccharomyces cerevisiae, any one of 5 genes, RAD1, RAD2, RAD3, RAD4, and RAD10, causes a total defect in the incision step of excision repair of DNA damaged by ultraviolet light and an extreme sensitivity to ultraviolet light. A high level of conservation was found in the COOH-terminal domain where the frequency of identical amino acids was about 50% with preservation of the zinc finger motif, suggesting that this portion of the gene plays an important role in the function of the protein. (1991) compared the homologous Xpa genes in chicken, Xenopus laevis, and Drosophila melanogaster with the human gene. Expression of XPA cDNA conferred UV resistance to several cells derived from patients with xeroderma pigmentosum complementation group A, but not with other XP complementation groups. A 1.0-1.1-kb mouse Xpa mRNA was also identified. Sequence analysis identified a truncated XPA protein that could be translated from an ATG present at position 176, which retained sufficient function to partially restore the DNA repair defect in XPA cells. Two mRNAs, 1.3-1.4 kb and 1.0-1.1 kb, were detected in normal human cells. The human protein is 95% similar to the mouse protein and contains several alpha-helices and a zinc-finger motif, consistent with a DNA-binding protein. The deduced 273-amino acid protein has a calculated molecular mass of 31 kD. (1990) cloned a cDNA corresponding to the human XPA gene. (1989) concluded that they had succeeded in cloning the mouse homolog of the gene that is mutant in XPA. No correction was observed in relation to other XP groups. ( 1989, 1990) cloned a mouse gene that restored UV light-resistance in 2 cell lines from patients with xeroderma pigmentosum complementation group A (XPA 278700).
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