Human chromosome 11 complements ataxia-telangiectasia cells but does not complement the defect in AT-like Chinese hamster cell mutants.
It has been shown that the X-ray-sensitive Chinese hamster V79 mutants (V-E5, V-C4 and V-G8) are similar to ataxia-telangiectasia (A-T) cells. To determine whether the AT-like rodent cell mutants are defective in the gene homologous to A-T (group A, C or D), human chromosome 11 was introduced to the V-E5 and V-G8 mutant cells by microcell-mediated chromosome transfer. Forty independent hybrid clones were obtained in which the presence of chromosome 11 was determined by in situ hybridization. The presence of the region of chromosome 11q22-23 was shown by molecular analysis using polymorphic DNA markers specific for the ATA, ATC and ATD loci. Seventeen of the obtained monochromosomal Chinese hamster hybrids contained a cytogenetically normal human chromosome 11, but only twelve hybrid cell lines were shown to contain an intact 11q22-23 region. Despite the complementation of the X-ray sensitivity by a normal chromosome 11 introduced to A-T cells (complementation group D), these twelve Chinese hamster hybrid clones showed lack of complementation of X-ray and streptonigrin hypersensitivity. The observed lack of complementation does not seem to be attributable to hypermethylation of the human chromosome 11 in the rodent cell background, since 5-azacytidine treatment had no effect on the streptonigrin hypersensitivity of the hybrid cell lines. These results indicate that the gene defective in the AT-like rodent cell mutants is not homologous to the ATA, ATC or ATD genes and that the human gene complementing the defect in the AT-like mutants seems not to be located on human chromosome 11.
Jongmans
W
W
MGC-Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, The Netherlands.
Wiegant
J
J
Oshimura
M
M
James
M R
MR
Lohman
P H
PH
Zdzienicka
M Z
MZ
D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002880:Chromosomes, Human, Pair 11; D006224:Cricetinae / Q000235:genetics*; D003412:Cricetulus; D005816:Genetic Complementation Test; D005838:Genotype; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011836:Radiation Tolerance / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013308:Streptonigrin / Q000494:pharmacology; D014162:Transfection / Q000379:methods
D013308:Streptonigrin