MutS Preferentially Recognizes Cisplatin- over Oxaliplatin-modified DNA

作者: Zoran Z. Zdraveski , Jill A. Mello , Christine K. Farinelli , John M. Essigmann , Martin G. Marinus

DOI: 10.1074/JBC.M105382200

关键词:

摘要: Loss of mismatch repair leads to tumor resistance by desensitizing cells specific DNA-damaging agents, including the anticancer drug cisplatin. Cisplatin analogs with a diamminocyclohexane (DACH) carrier ligand, such as oxaliplatin and Pt(DACH)Cl(2), do not elicit in repair-deficient therefore present promising therapeutic agents. This study compared interactions purified Escherichia coli protein MutS DNA modified contain cisplatin DACH adducts. recognized cisplatin-modified 2-fold higher affinity comparison DACH-modified DNA. ADP stimulated binding DNA, whereas it had no effect on interaction or EN In parallel cytotoxicity experiments, methylation-deficient E. dam mutants were more sensitive than compounds. A panel recombination-deficient showed striking sensitivity both compounds, indicating that types adducts are strong replication blocks. The differential for different platinum could provide molecular basis distinctive cellular responses oxaliplatin.

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