Topological differences in the interaction of human DNA topoisomerase I with DNA-histone complexes modified by cis- and trans-DDP.
We show that the trefoil, figure-eight knot, and mini circular closed DNA are formed by the reaction of cis-DDP-modified psiX174DNA-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 psiX174DNA-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.
Kobayashi
Shigeki
S
Division of Analytical Chemistry of Medicines, Showa Pharmaceutical University, Tokyo, Japan. kobayasi@ac.shoyaku.ac.jp
Koyama
Yuhki
Y
D000970:Antineoplastic Agents / Q000737:chemistry*; D010584:Bacteriophage phi X 174 / Q000235:genetics; D002945:Cisplatin / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D004279:DNA, Viral / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008854:Microscopy, Electron; D009690:Nucleic Acid Conformation
D000970:Antineoplastic Agents; D004279:DNA, Viral; D006657:Histones; D004264:DNA Topoisomerases, Type I; D002945:Cisplatin