Topology effect for DNA structure of cisplatin: topological transformation of cisplatin-closed circular DNA adducts by DNA topoisomerase I

Chem Pharm Bull (Tokyo). 1999 Jun;47(6):783-90. doi: 10.1248/cpb.47.783.

Abstract

The reaction of cis-Pt(NH3)2Cl2(cis-DDP)-closed circular DNA adducts with DNA topoisomerse I(topo I) were studied by electron microscopy. We identified unique topoisomers such as a singly-linked catenane (2(1)2), trefoil (3(1), and dimetric catenane (2(1)2), etc., by analysis with electron micrographs. These unique recombination products resulted from cis-DDP-intra-twisting looped DNA adducts by DNA topo I, and the products could be explained a new mechanism based on an odd-even number rule. Our results suggest a new model on the working mechanisms for DNA topology of cis-DDP which enhances the recombination of DNA. Based on our results, we propose the topological idea that the yields of a mini closed circular DNA and pseudo trefoil DNA, etc., can be expected by reaction of cis-DDP-DNA-histone complexes with DNA topo I in the body.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cisplatin / chemistry*
  • Cisplatin / pharmacology*
  • DNA Adducts / chemistry*
  • DNA Topoisomerases, Type I / drug effects
  • DNA Topoisomerases, Type I / metabolism
  • DNA, Circular / chemistry
  • DNA, Circular / drug effects*
  • DNA, Circular / ultrastructure
  • Electrophoresis, Agar Gel
  • Isomerism
  • Microscopy, Electron
  • Nucleic Acid Conformation
  • Recombination, Genetic / drug effects

Substances

  • Antineoplastic Agents
  • DNA Adducts
  • DNA, Circular
  • DNA Topoisomerases, Type I
  • Cisplatin