Repair of cis-platinum-DNA adducts by ABC excinuclease in vivo and in vitro.
cis-Platinum compounds, which are used in cancer chemotherapy, are thought to exert their effect by damaging DNA. It is known that this damage is partially repaired in Escherichia coli. Using cis-Pt-treated pBR322 DNA as a probe, we investigated the role of nucleotide excision repair in the removal of Pt-DNA adducts. We found that the nucleotide excision pathway was the major mechanism for repairing Pt adducts in transforming plasmid DNA but that a recA-dependent pathway also contributed to plasmid survival. When cis-Pt-damaged pBR322 was treated with the purified nucleotide excision enzyme ABC excinuclease in vitro, a fraction of the adducts was removed by the enzyme; this removal resulted in a corresponding increase in transformation efficiency.
D002945:Cisplatin / Q000378:metabolism*; D004260:DNA Repair; D004269:DNA, Bacterial / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D029968:Escherichia coli Proteins; D007700:Kinetics; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D010641:Phenotype; D010957:Plasmids / Q000187:drug effects
D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D009944:Organoplatinum Compounds; C013933:dichloro-1,2-diaminocyclohexane platinum complex; D004706:Endodeoxyribonucleases; C036385:endodeoxyribonuclease uvrABC; D002945:Cisplatin