Norfloxacin-induced DNA cleavage occurs at the dif resolvase locus in Escherichia coli and is the result of Interaction with topoisomerase IV

The dif locus is a site-specific recombination site located within the term inus region of the chromosome of Escherichia coil. Recombination at dif res olves circular dimer chromosomes to monomers, and this recombination requir es the XerC, XerD and FtsK proteins, as well as cell division. In order to characterize other enzymes that interact at dif,we tested whether quinolone -induced cleavage occurs at this site. Quinolone drugs, such as norfloxacin , inhibit the type 2 topoisomerases, DNA gyrase and topoisomerase IV, and c an cleave DNA at sites where these enzymes interact with the chromosome. Us ing strains in which either DNA gyrase or topoisomerase IV, or both, were r esistant to norfloxacin, we determined that specific interactions between d if and topoisomerase IV caused cleavage at that site. This interaction requ ired XerC and XerD, but did not require the C-terminal region of FtsK or ce ll division.