Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fluoroquinolone ciprofloxacin, an inhibitor of eubacterial DNA gyrase, induces single- and double-stranded DNA breaks in the plasmid pGRB-1 from the halophilic archaebacterium Halobacterium GRB when the cells are treated by this drug in a magnesium-depleted medium. This reaction is prevented by a dose of novobiocin known to specifically inhibit DNA gyrase. Cleavage of pGRB-1 DNA induced by either ciprofloxacin or the antitumoral drug etoposide (VP16) produces DNA fragments of identical lengths. These results indicate that ciprofloxacin, novobiocin, and etoposide have a common target in Halobacterium GRB: an archaebacterial type II DNA topoisomerase. The similarity of DNA cleavage patterns induced by ciprofloxacin and etoposide is a new and strong argument that quinolone and epipodophyllotoxins have the same mode of interaction with the DNA-DNA topoisomerase II complexes. The plasmid pGRB-1 could be used to prescreen in the same system both antibiotics that inhibit bacterial gyrase and antitumoral drugs that inhibit eukaryotic DNA topoisomerase II.
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PMID:Ciprofloxacin and etoposide (VP16) produce a similar pattern of DNA cleavage in a plasmid of an archaebacterium. 275 86

Treatment of Halobacterium GRB cells with the DNA topoisomerase II inhibitor novobiocin induces the accumulation of a circular single-stranded DNA form of the plasmid pGRB-1. This form corresponds to the transcribed strand of pGRB-1. A tiny amount of this form is detectable in untreated cells. The induction of single-stranded pGRB-1 molecules by novobiocin is abolished when cells are pretreated with aphidicolin or anisomycin, which inhibit halobacterial DNA replication and protein synthesis, respectively. These results suggest that the single-stranded form of pGRB-1 is generated in the course of plasmid replication.
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PMID:Novobiocin induces accumulation of a single strand of plasmid pGRB-1 in the archaebacterium Halobacterium GRB. 341 1

The topoprofile of 1.7 kb plasmids from the archaebacterium Halobacterium GRB was analysed from cells growing with or without VP16 (etoposide). This drug interferes with the breakage-reunion reaction of eukaryotic DNA topoisomerase II by inhibiting the ligase activity of this enzyme. Addition of VP16 to the culture medium of Halobacterium GRB cells results in the introduction of single- and double-strand DNA breaks in part of the plasmid population, with proteins covalently associated at their 5' ends. While some of the remaining covalently closed circular DNA molecules are relaxed, VP16 treatment also gives rise to the production of positively supercoiled 1.7 kb plasmids. In contrast to adriamycin, VP16 does not intercalate into the 1.7 kb plasmid DNA in vivo. These results suggest that the VP16 target in halobacteria is a DNA topoisomerase II. Three major cleavage sites were detected on the 1.7 kb plasmid after VP16 treatment in vivo.
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PMID:Effects of the antitumor drug VP16 (etoposide) on the archaebacterial Halobacterium GRB 1.7 kb plasmid in vivo. 367 Oct 82

The two DNA intercalators, actinomycin D and 2-methyl-9-hydroxy-ellipticine, and the DNA minor groove ligant DAPI inhibited the growth of the haloarchaeon Halobacterium sp. GRB and bind to its plasmid pGRB-1. In contrast to specific DNA topoisomerase II inhibitors, they produced neither double-stranded breaks nor relaxation of plasmidic DNA. The two DNA intercalators inhibited positive supercoiling induced by novobiocin, suggesting that positive supercoiling in haloarchaea is due to transcription, as in the domain Bacteria. Plasmids from haloarchaea could thus be used to prescreen for DNA intercalators and to discriminate between different drug families via their mode of action.
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PMID:DNA intercalating drugs inhibit positive supercoiling induced by novobiocin in halophilic archaea. 798 84