Induction of duplication reversion in human fibroblasts, by wild-type and mutated SV40 T antigen, covaries with the ability to induce host DNA synthesis.
Intrachromosomal homologous recombination, manifest as reversion of a 14-kbp duplication in the hypoxanthine phosphoribosyl transferase (HPRT) gene, is elevated in human cells either stably transformed or transiently transfected by the SV40 (simian virus 40) large T antigen gene. Following introduction of wild-type SV40, or any of several T-antigen point mutations in a constant SV40 background, we observed a strong correlation between the stimulation of chromosomal recombination and induction of host-cell DNA synthesis. Moreover, inhibitors of DNA replication (aphidicolin and hydroxyurea) suppress SV40-induced homologous recombination to the extent that they suppress DNA synthesis. Stable integration of plasmids encoding T antigen also augments homologous recombination, which is suppressed by aphidicolin. We infer that the mechanism by which T antigen stimulates homologous recombination in human fibroblasts involves DNA replicative synthesis.
Shammas
M A
MA
Department of Biochemistry, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Xia
S J
SJ
Shmookler Reis
R J
RJ
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D016590:Aphidicolin / Q000494:pharmacology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts; D005814:Genes, Viral; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D005810:Multigene Family; D009154:Mutation; D011995:Recombination, Genetic; D013539:Simian virus 40 / Q000235:genetics; D014162:Transfection; D014170:Transformation, Genetic; D015678:Viral Structural Proteins / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D015678:Viral Structural Proteins; D016590:Aphidicolin; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase; D006918:Hydroxyurea