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 terminus region of the chromosome of Escherichia coli. Recombination at dif resolves circular dimer chromosomes to monomers, and this recombination requires 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 can cleave DNA at sites where these enzymes interact with the chromosome. Using strains in which either DNA gyrase or topoisomerase IV, or both, were resistant to norfloxacin, we determined that specific interactions between dif and topoisomerase IV caused cleavage at that site. This interaction required XerC and XerD, but did not require the C-terminal region of FtsK or cell division.
Hojgaard
A
A
Department of Pathology, University of Utah, Salt Lake City 84112, USA.
Szerlong
H
H
Tabor
C
C
Kuempel
P
P
D000890:Anti-Infective Agents / Q000494:pharmacology*; D027081:DNA Gyrase; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D029968:Escherichia coli Proteins; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009643:Norfloxacin / Q000494:pharmacology*; D045522:Recombinases; D019895:Transposases / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism
D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; C096452:FtsK protein, E coli; D008565:Membrane Proteins; D045522:Recombinases; D019895:Transposases; C034510:CTCGAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; C024400:GTYRAC-specific type II deoxyribonucleases; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II; D009643:Norfloxacin