Topological Differences in the Interaction of Human DNA Topoisomerase I with DNA-Histone Complexes Modified by cis- and trans-DDP

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We show that the trefoil, figure-eight knot, and mini circular closed DNA are formed by the reaction of cis-DDP-modified φX174DNA-histone^<LNCap> complexes as a new nucleosome model with human DNA topoisomease I. The yields from cis-DDP-modified complexes were far higher than that of trans-DDP. The topologically-distinct invariant DNA such as the trefoil and figure-eight knot are not produced in the reaction of DNA topo I with φX174DNA-histone^<LNCap> complexes that are not modified by platinum. Therefore, the anti-cancer activity of cis-DDP may be related to the production of the trefoil, figure-eight knot, and mini circular closed DNA forms in the living cell. We subsequently demonstrate that the yield mechanism and identification of the topologically-distinct invariant DNA can be explained by the topological method using a Jones polynomial and recombination through the topo I path intra-twisted looped DNA model. These results suggest that the distinguishing of anti-neoplastic activity of cis- and trans-DDP can be partially explained by the distinct topologies of DNA, trefoil, figure-eight knot, and mini circular closed DNA that they produce.
2007-04-01