Integration of simian virus 40 into cellular DNA occurs at or near topoisomerase II cleavage hot spots induced by VM-26 (teniposide).
Inhibition of DNA topoisomerase II in simian virus 40 (SV40)-infected BSC-1 cells with a topoisomerase II poison, VM-26 (teniposide), resulted in rapid conversion of a population of the SV40 DNA into a high-molecular-weight form. Characterization of this high-molecular-weight form of SV40 DNA suggests that it is linear, double stranded, and a recombinant with SV40 DNA sequences covalently joined to cellular DNA. The majority of the integrants contain fewer than two tandem copies of SV40 DNA. Neither DNA-damaging agents, such as mitomycin and UV, nor the topoisomerase I inhibitor camptothecin induced detectable integration in this system. In addition, the recombination junctions within the SV40 portion of the integrants correlate with VM-26-induced, topoisomerase II cleavage hot spots on SV40 DNA. These results suggest a direct and specific role for topoisomerase II and possibly the enzyme-inhibitor-DNA ternary cleavable complex in integration. The propensity of poisoned topoisomerase II to induce viral integration also suggests a role for topoisomerase II in a pathway of chromosomal DNA rearrangements.
Bodley
A L
AL
Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.
Huang
H C
HC
Yu
C
C
Liu
L F
LF
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D004247:DNA; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D000882:Haplorhini; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015183:Restriction Mapping; D013539:Simian virus 40 / Q000502:physiology*; D013713:Teniposide / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors; D016662:Virus Integration; D014779:Virus Replication
D059005:Topoisomerase II Inhibitors; D004247:DNA; D013713:Teniposide; D004250:DNA Topoisomerases, Type II