The effect of binding of cis-diamminedichloroplatinum(II), its trans isomer and diethylenetriaminechloroplatinum(II) chloride to DNA on the splicing effectiveness of BamHI, EcoRI and SalI restriction endonucleases has been determined by means of gel electrophoresis. All three platinum complexes inhibit the cleavage of linearized plasmid DNA. In addition, the three platinum complexes bound to DNA constitute a barrier across which the linear diffusion of EcoRI on DNA is difficult. We interpret these findings to mean that the splicing effectiveness of restriction enzymes is influenced by bifunctional and monofunctional DNA adducts of platinum via both steric interference and DNA conformational distortions. Whereas the platinum adducts in the restriction sites or in their very close proximity inhibit the cleavage, the lesions occurring a greater distance from the restriction site can slow down the process of the localization of recognition sequences.
- MeSH
- Cisplatin pharmacology MeSH
- Deoxyribonuclease BamHI metabolism MeSH
- Deoxyribonuclease EcoRI metabolism MeSH
- DNA metabolism MeSH
- Electrophoresis, Agar Gel MeSH
- Organoplatinum Compounds pharmacology MeSH
- Plasmids drug effects MeSH
- Deoxyribonucleases, Type II Site-Specific metabolism MeSH
- Stereoisomerism MeSH
- Binding Sites MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
- Names of Substances
- Cisplatin MeSH
- Deoxyribonuclease BamHI MeSH
- Deoxyribonuclease EcoRI MeSH
- DNA MeSH
- GTCGAC-specific type II deoxyribonucleases MeSH Browser
- Organoplatinum Compounds MeSH
- Deoxyribonucleases, Type II Site-Specific MeSH
The effect of binding of an antitumour drug cis-diamminedichloroplatinum(II) (cis-[Pt(NH3)2Cl2]) to DNA on cutting effectiveness of BamHI, EcoRI, and SalI restriction endonucleases was quantitatively determined. The platinum complex inhibits the cleavage of plasmid pHC624 DNA linearized by BglI restrictase. From the present results we conclude that the yield of restriction endonuclease cleavage is also lowered if the platinum complex is bound outside the recognition DNA sequence of these enzymes. We propose that the origin of platinum adducts on DNA outside the recognition sequence can decrease the yield of restriction enzyme cleavage via inducing a conformational perturbation in the recognition DNA sequence of these enzymes and also via inhibition of the linear diffusion of these enzymes on DNA.
- MeSH
- Cisplatin chemistry pharmacology MeSH
- DNA chemistry drug effects genetics MeSH
- Molecular Sequence Data MeSH
- Plasmids MeSH
- DNA Restriction Enzymes MeSH
- Base Sequence MeSH
- Binding Sites MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cisplatin MeSH
- DNA MeSH
- DNA Restriction Enzymes MeSH
