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Nucleic Acids Research, 1992, Vol. 20, No. 15 4033-4038
© 1992

MOLECULAR BIOLOGY

Ellipticine increase the superhelical density of intracellular SV40 DNA by intercalation

Yi chu and Ming-Ta Hsu1,*

Division of Cardiology, Vandebilt University School of Medicine Nashville, TN 37232-2170 10029, USA 1Institute of Biomedical Sciences. Academia Sinica Taiwan, china

*To whom Correspondence should be addressed

Received April 7, 1992. Revised June 3, 1992. We investigated the in vivo effect of ellipticine, a mammalian topoisomerasell(topoll) inhibitor, on SV40 DNA topology. In contrast to epipodophyllotoxins, ellipticine did not cause significant double stranded cleavage of intracellular SV40 DNA. Furthermore, ellipticine reduced cleavage Induced by epipodophyllotoxins, VP16 and VM26. Unexpectedly, ellipticine dramatically increased the superhelical density of a fraction of intracellular SV40 DNA. Several lines of evidence suggest that the formation of this highly supercoiled DNA species (Ih form DNA) is not due to the inhibition of topoll per se, but is the result of intercalation by ellipticine in a subtraction of the intracellular SV40 chromatin followed by the fixation of DNA linking number by a topolsomerase activity. Based on the linking number change and the known unwinding angle of ellipticine, the intercalation density was calculated as one ellipticine molecule per 10-20 bp in the Ih DNA. This result suggests the existence of different populations of intracellular SV40 chromatin with respect to the accessibility to ellipticine Intercalation.


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