MOLECULAR-CLONING AND STRUCTURAL-ANALYSIS OF THE FUNCTIONAL-MOUSE GENOMIC XPG GENE

The mouse XPG gene is a homolog of the human DNA excision repair gene known to be defective in the hereditary sun-sensitive disorder xeroder ma pigmentosum (group-G). Defects in mouse XPG have been shown to dire ctly affect the sensitivity of cultured cells to chemotherapy agents a nd may play a role in tumor cell drug resistance bl vivo. A full-lengt h cosmid clone of mouse XPG was isolated by complementation of the UV sensitivity and repair defect in CHO-UV135 cells. Exon mapping determi ned that the gene consisted of 15 exons within 32 kb of genomic DNA. S equencing of intron-exon boundaries revealed that mouse XPG possesses a rare class of intron previously identified in only four other eukary otic genes; it utilizes AT and AC dinucleotides instead of the expecte d GT and AG within the splice junctions. Promoter analysis determined that mouse XPG is expressed constitutively and probably initiates tran scription from multiple start sites, yet, unlike the yeast homolog RAD 2, we found no evidence that it is WC inducible in cultured cells. Ami no acid comparison with human XPG identified a highly conserved acidic region of homology not previously described.