Intrachromosomal recombination mediated by papovavirus large T antigens.
To investigate the mechanism by which the large T antigen (T-Ag) of polyomavirus and simian virus 40 can promote recombination in mammalian cells, we analyzed homologous recombination events occurring between two defective copies of the polyomavirus middle T (pmt) oncogene lying in close proximity on the same chromosome in a rat cell line. Reconstitution of a functional pmt gene by spontaneous recombination occurred at a rate of about 2 x 10(-7) per cell generation. Introduction of the polyomavirus large T (plt) oncogene into the cell line by DNA transfection promoted recombination very efficiently, with rates in the range of 10(-1) to 10(-2) per cell generation. Recombination was independent of any amplification of viral sequences and could even be promoted by the large T-Ag from simian virus 40, which cannot activate polyomavirus DNA replication. To explain the role of large T-Ag, we propose a novel mechanism of nonconservative recombination involving slipped-strand mispairing between the two viral repeats followed by gap repair synthesis.
St-Onge
L
L
Department of Microbiology, University of Sherbrooke, Quebec, Canada.
Bouchard
L
L
Laurent
S
S
Bastin
M
M
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D015139:Blotting, Southern; D002460:Cell Line; D002875:Chromosomes / Q000502:physiology; D004261:DNA Replication; D004251:DNA Transposable Elements; D003673:Defective Viruses / Q000235:genetics; D009154:Mutation; D009857:Oncogenes; D010957:Plasmids; D011120:Polyomavirus / Q000235:genetics* / Q000276:immunology; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D015183:Restriction Mapping; D013539:Simian virus 40 / Q000235:genetics* / Q000276:immunology
D000952:Antigens, Polyomavirus Transforming; D004251:DNA Transposable Elements