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Plasmid DNA including the simian virus 40 (SV40) origin of replication undergoes uncontrolled, runaway replication in cos-1 cells owing to the intracellular production of SV40 large T antigen. Covalent linkage of such plasmids with human papillomavirus type 16 (HPV-16) DNA was found to prevent runaway replication. Replication control was found to be dependent on the presence of HPV-16 DNA sequences including the E1 open reading frame and part of the non-coding region.
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