Disease relevance of novobiocin

• Since novobiocin is known to reduce torsional stress in E. coli DNA, we interpret our results to mean that PA is regulated by torsional stress in the chloroplast DNA [1].
• Effect of novobiocin on initiation of DNA replication in Bacillus subtilis [2].
• Novobiocin inhibition of simian virus 40 DNA replication [3].
• Cloning and characterization of a DNA gyrase B gene from Streptomyces sphaeroides that confers resistance to novobiocin [4].
• We have isolated a mycolate-deficient mutant strain of Mycobacterium smegmatis mc2-155 by chemical mutagenesis followed by screening for increased sensitivity to novobiocin [5].

High impact information on novobiocin

• We have characterized regulation of a complex Chlamydomonas reinhardtii chloroplast (PA) whose activity is stimulated by the DNA gyrase inhibitor novobiocin, both in the alga itself and in a heterologous Escherichia coli plasmid system [1].
• Novobiocin stimulates PA only when the promoter-distal silencing element is present [1].
• The chromatin assembled with TFIIIA is dynamic and rapidly relaxed by novobiocin; the chromatin assembled without TFIIIA is static and unaffected by novobiocin [6].
• DNA gyration also requires the oocyte supernatant, ATP, and Mg2+, and is inhibited by novobiocin, suggesting that it is catalyzed by a type II DNA topoisomerase [6].
• We find that when chicken red blood cells are incubated in media containing the topoisomerase II inhibitor novobiocin, the preferential DNAase I sensitivity of the active beta-globin genes is reversed in vivo with as little as 20 min of drug treatment [7].

Chemical compound and disease context of novobiocin

• Gene expression changes triggered by exposure of Haemophilus influenzae to novobiocin or ciprofloxacin: combined transcription and translation analysis [8].
• PATIENTS AND METHODS: Thirty-eight women with responsive metastatic breast cancer received high-dose cyclophosphamide (3 to 6 g/m2 over 4 days), thiotepa (400 to 800 mg/m2), and novobiocin (0.5 to 5.0 g/d x 7, orally) with autologous marrow support [9].
• Study aims were to define the toxicities and maximal-tolerated dose (MTD) of novobiocin and the pharmacokinetics of novobiocin and high-dose cyclophosphamide and thiotepa [9].
• Just as with the regenerating rat liver polymerases, the 3 S activity of a bronchogenic carcinoma is unaffected by cytosine arabinoside 5'-triphosphate and only little reduced by novobiocin, whereas DNA synthesis by the 7 S enzyme is abolished by both compounds [10].
• Phase I and pharmacologic study of the alkylating agent modulator novobiocin in combination with high-dose chemotherapy for the treatment of metastatic breast cancer [9].

Biological context of novobiocin

• We found that the addition of certain antibiotics in the growth medium, such as novobiocin which inhibits DNA replication, fulfills these requirements, allowing proinsulin synthesis and excretion to take place over a period of several days [11].
• We have found that only a limited segment of the chromosome at the origin region was replicated in the presence of novobiocin [2].
• Hydroxyurea, novobiocin and aphidicolin, inhibitors of ribonucleotide reductase, topoisomerase and DNA polymerase alpha, respectively, all inhibit thymidylate synthase in intact S phase CHEF/18 cells, but not in their soluble extracts [12].
• Nalidixic acid and novobiocin inhibit the aminoacylation and pyrophosphate exchange activities of glycyl- and leucyl-transfer RNA synthetases from bakers' yeast [13].
• Novobiocin inhibits passive chromatin assembly in vitro [14].

Anatomical context of novobiocin

• Furthermore, novobiocin reduced Raf-1 levels in the spleens of mice treated with the drug [15].
• Novobiocin and anti-calf thymus DNA topoisomerase II antibody inhibit this ATP-dependent recombination [16].
• The inhibition by novobiocin of colicin E1 plasmid DNA replication in a cell-free system is partially relieved by adding resistant DNA gyrase [17].
• We discovered a new biological activity of the well-known coumarin antibiotic novobiocin; the treatment of eukaryotic cells with novobiocin induces the rapid depletion of PrPc [18].
• Furthermore, exposure of both cell lines to novobiocin did not affect intracellular ATP levels [19].

Associations of novobiocin with other chemical compounds

• Addition of nalidixic acid (an inhibitor of gyrase subunit A) and novobiocin (an inhibitor of gyrase subunit B) to an in vitro system capable of synthesizing phi X174 viral DNA inhibited DNA synthesis [20].
• The results demonstrate that the levels of mRNA for light-harvesting (I, II) and reaction center (L, M, H) proteins, bacteriochlorophyll biosynthetic enzymes, ribulose-bisphosphate carboxylase (EC 4.1.1.39), and the mRNAs from the open reading frames Q and R decreased immediately and dramatically upon addition of novobiocin and coumermycin [21].
• Replication of plasmid DNA in this system is semiconservative and sensitive to actinomycin D, novobiocin, arabinofuranosyl-CTP,N-ethylmaleimide, and inhibitors of DNA-dependent RNA polymerase [22].
• Exponentially growing Chinese hamster ovary cells, exposed to inhibitors of topoisomerase II (novobiocin, nalidixic acid, etoposide, and 4'-(9-acridinylamino)methanesulfon-m-anisidide were blocked in progression through G2 [23].
• These actions of novobiocin and butyrate were not mediated by the pathway of epidermal growth factor action or modulated by the diacylglycerol agonist 1-oleoyl-2-acetylglycerol and the C kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine [24].

Gene context of novobiocin

• Evidence that this promoter coupling is DNA supercoiling-dependent is provided by the observation that a novobiocin-induced decrease in global negative superhelicity results in an increase in ilvY promoter activity and a decrease in ilvC promoter activity predicted by the in vitro data [25].
• Treatment of cells with either geldanamycin or novobiocin, two pharmacological inhibitors of Hsp90 causes the destabilization of LKB1 [26].
• Expression and analysis of two gyrB genes from the novobiocin producer, Streptomyces sphaeroides [27].
• The mukB mutant was oversensitive to novobiocin and this susceptibility was suppressed in the mukBseqA strain, suggesting possible roles of MukB and SeqA in maintaining chromosome topology [28].
• Transcription from the fimA promoter was unaffected by changes in DNA supercoiling whether caused by the introduction of a topA::Tn10 mutation or by inhibition of DNA gyrase with the antibiotic novobiocin [29].

Analytical, diagnostic and therapeutic context of novobiocin

• Partial purification of DNA gyrase by affinity chromatography revealed the presence of two such activities (differing in their responses to novobiocin) in the clone [4].
• The acquisition of maturation markers and changes in the activity, level, and phosphorylation of Topo II were determined after treatment with either novobiocin, a Topo II inhibitor, or PMA [30].
• Plasma novobiocin levels > or = 100 micrograms/mL, which are associated with reversal of drug resistance in animal models, were consistently seen at dose levels greater than 2 g [9].
• It has also been suggested that novobiocin-induced inhibition of repair is mediated by alterations of chromatin structure recognizable by electron microscopy as gross chromatin clumping [31].
• The water-mediated hydrogen bonds linking novobiocin to the mutant protein make a favorable enthalpic contribution, whereas the immobilization of the water leads to an entropic cost and a reduction in the heat capacity of the system [32].

References