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Lambert B , Jestin JL , Brehin P , Oleykowski C , Yeung AT , Mailliet P , Pretot C , Lepecq JB , Jacqueminsablon A , Chottard JC
Binding of the Escherichia-Coli Uvrab Proteins to the DNA Monoadducts and Diadducts of Cis- N-2-Amino-N-2-Methylamino- 2,2,1-Bicycloheptane Dichloroplatinum(Ii) and Cisplatin - Analysis of the Factors Controlling Recognition and Proof of Monoadduct-Mediated Uvrb-DNA Cross-Linking
Journal of Biological Chemistry. 1995 Sep 8;270(36) :21251-21257
PMID: ISI:A1995RU05400059   
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The interactions of the Escherichia coli endonuclease UvrAB proteins with the DNA mono- and diadducts of both the cis- racemic exo-[N-2-amino-N-2-methylamino-2,2,1- bicycloheptane]dichloroplatinum(II (complex (1) under bar) and cisplatin (cis-diamminedichloroplatinum(II) (cis-DDP)), have been studied, Complex (1) under bar reacts faster with DNA than cis-DDP and gives monoadducts with a longer lifetime (8 h 20 min chelation t(1/2) compared with 2 h 40 min for cis-DDP), Using pSP65 plasmid [H-3]DNA, the filter binding assay was associated with the analysis of the nucleoprotein complexes to characterize the UvrAB recognition of the platinum adducts and to demonstrate the occurrence of platinum-mediated DNA-protein cross-linking, First, it is shown that the UvrAB proteins recognize the complex (1) under bar mono- and diadducts with a higher affinity than those of cis-DDP. Fifteen times more cis- DDP adducts per plasmid are required than complex (1) under bar adducts, to lead to similar UvrAB binding, However, the UvrAB proteins recognize monoadducts and diadducts of each complex with a similar affinity, Second, it is shown that UvrB is the protein involved in the nucleoprotein complexes formed from mono- and diadducts of complex (1) under bar and cis-DDP, This protein is also partly cross-linked to DNA with a similar efficiency by monoadducts derived from complex (1) under bar and cis-DDP, However, as UvrB has a greater affinity for the DNA adducts of complex (1) under bar than for those of cis-DDP, more UvrB-platinum-DNA cross-links are formed with complex 1 than with cis-DDP, This study, using a bacterial repair system as a model, points to a possible strategy for making new cytotoxic platinum complexes for mammalian cells.
Times Cited: 10 Article RU054 J BIOL CHEM