Complementation of a DNA repair defect in xeroderma pigmentosum cells by transfer of human chromosome 9.

Abstract

Complementation of the repair defect in xeroderma pigmentosum cells of complementation group A was achieved by the transfer of human chromosome 9. A set of mouse-human hybrid cell lines, each containing a single Ecogpt-marked human chromosome, was used as a source of donor chromosomes. Chromosome transfer to XPTG-1 cells, a hypoxanthine/guanine phosphoribosyltransferase-deficient mutant of simian virus 40-transformed complementation group A cells, was achieved by microcell fusion and selection for Ecogpt. Chromosome-transfer clones of XPTG-1 cells, each containing a different human donor chromosome, were analyzed for complementation of sensitivity to UV irradiation. Among all the clones, increased levels of resistance to UV was observed only in clones containing chromosome 9. Since our recipient cell line XPTG-1 is hypoxanthine/guanine phosphoribosyltransferase deficient, cultivation of Ecogpt+ clones in medium containing 6-thioguanine permits selection of cells for loss of the marker and, by inference, transferred chromosome 9. Clones isolated for growth in 6-thioguanine, which have lost the Ecogpt-marked chromosome, exhibited a UV-sensitive phenotype, confirming the presence of the repair gene(s) for complementation group A on chromosome 9.

The manipulation of chromosomes by mankind: the uses of microcell-mediated chromosome transfer

“…This had led to genes on human chromosome 9 (Kaur and Athwal 1989), chromo- (Kaur and Athwal 1993), being able to complement specific group defects. For ataxia-telangiectasia complementation genes and chromosomal regions for DNA repair have been found by MMCT to be on chromosome 11 (Kodama et al 1992), indeed 11q22-23 (Lambert et al 1991).…”

Report of the committee on the genetic constitution of chromosome 9

“…The complementation of a DNA repair deficiency in xeroderma pigmentosum cells from complementation group A by transfer of human chromosome 9 allows the provisional assignment of XPA to this chromosome (Kaur and Athwal, 1989). Further evidence for the cloning of the gene and its assignment to 9q22-32 is quoted in a review article by Cleaver (1990), although the primary data were not available to this committee.…”

Report of the committee on linkage and gene order

“…Also localized on 5q was a gene for diastrophic dysplasia (DTD) (Hastbacka ct al., 1990). The gene for xeroderma pigmentosum (XP) has been assigned to chromosome 9 (Kaur and Athwal, 1989). Chronic granulomatous disease (NCF1), previously incorrectly mapped to chromosome 10, is now on chromosome 7 (Francke et al, 1990).…”