Disease relevance of Phleomycin

• The effects of changes in the conformational state of DNA on the single-strand and double-strand breakage activity of two antitumor antibiotics, bleomycin (BLM) A2 and phleomycin D1, have been studied by the gel electrophoretic analysis of the drug-degraded PM2 phage superhelical DNA pretreated with an intercalating agent, ethidium bromide (EB) [1].
• A study, by sedimentation methods, of DNA single-strand breakage in phleomycin-treated E. coli cells, using 3 representative compounds, Crystal Violet, 3,6-diaminoacridine and Methylene Blue, revealed a consistent increase in DNA strand breaks as concentration of compound increased [2].
• Inhibition of bacteriophage PBS2 replication in Bacillus subtilis by phleomycin [3].
• Induction of alkaline phosphatase in choriocarcinoma cells by 1-beta-D-arabinofuranosyl-cytosine, mitomycin C, phleomycin, and cyclic nucleotides [4].
• Cyclase yeast transformants were screened using the Zeocin (phleomycin from Streptomyces verticillus) selectable marker which resulted in 100% active transformation [5].

High impact information on Phleomycin

• Antibiotic-resistance markers also were used to tag the a gene complex in MAT-1 strains (phleomycin) and the b gene complex in MAT-2 strains (hygromycin) [6].
• Multiple DSBs were created either by expressing the HO endonuclease in strains containing several HO cut sites embedded within randomly dispersed Ty1 elements or by phleomycin treatment [7].
• Activation of a ble-tagged 300-kb chromosome could not be achieved, but phleomycin-resistant clones could be obtained [8].
• We inserted the drug resistance genes neo and ble, conferring resistance to G418 and phleomycin, respectively, 1 kb downstream of "silent" ES promoters [8].
• Cleavage of cellular and extracellular Saccharomyces cerevisiae DNA by bleomycin and phleomycin [9].

Chemical compound and disease context of Phleomycin

• An Escherichia coli mutant resistant to phleomycin, bleomycin, and heat inactivation is defective in ubiquinone synthesis [10].
• Neither Ku70- nor Ku80-disrupted strains show hypersensitivity to the DNA damaging agents methylmethane sulfonate (MMS) and phleomycin [11].

Biological context of Phleomycin

• Control of in vivo (cellular) phleomycin sensitivity by nuclear genotype, growth phase, and metal ions [12].
• Stationary-phase haploid yeast cells were more sensitive than exponentially growing cells to killing by phleomycin [12].
• Mutants exhibiting sensitivities to phleomycin similar to normal strains of the same ploidy were sensitive to ultraviolet radiation [12].
• Here, we describe another phosphorylation event on serine 1 (S1) of histone H4; this event is also associated with MMS- or phleomycin-induced DSBs but not with UV-induced DNA damage [13].
• The phleomycin resistance gene was inserted in the place of the gag-pol genes on a plasmid expressing the env gene [14].

Anatomical context of Phleomycin

• Placed under the control of the strong CMV promoter, these constructs induced intense ADH substrate staining and phleomycin resistance, whatever the position of the ADH gene, in avian or mammalian cell lines [15].
• In wild-type cells this chimeric protein is imported into the peroxisome, which prevents the neutralizing interaction of the chimeric protein with its toxic phleomycin ligand [16].
• Stationary-phase Escherichia coli B cells transferred to new growth medium are initially resistant to net DNA breakage by low concentrations of phleomycin, and become sensitive as DNA replication commences [17].
• Linearised pAN7-1 DNA transformed phleomycin-resistant protoplasts at higher frequencies still [18].
• The linearized gene trap vector was introduced into mouse embryonic stem cells (ES cells), and 40 phleomycin resistant (phleo') cell lines possessing a single copy of the insert were selected [19].

Associations of Phleomycin with other chemical compounds

• Chromosomes were cleaved into nucleosomes and degraded by phleomycin over substantially narrower dose ranges (1 to 2 x 10(-6) M) than by bleomycin (about 1 to 17 x 10(-5) M) [20].
• Bleomycin B2, tallysomycin, and phleomycin were the most potent growth inhibitors, and bleomycin B2 caused the most DNA damage [21].
• Some of these characteristics, together with mapping data, suggested that the phleomycin resistance and Suc- determinant probably lies within the ubiF gene coding for an enzyme effecting a step in the biosynthesis of ubiquinone [10].
• Deletion mutants of CHL1 or CTF4, which are required for sister chromatid cohesion, showed higher sensitivity to the DNA damaging agents methyl methanesulfonate (MMS), hydroxyurea (HU), phleomycin, and camptothecin, similar to the phenotype of mutants of RAD52, which is essential for recombination repair [22].
• The ubiCA mutant exhibited a pleiotropic phenotype, being resistant to heat, linolenic acid and phleomycin [23].

Gene context of Phleomycin

• Vectors that confer high levels of phleomycin (Ph) resistance to Saccharomyces cerevisiae have been constructed with the TEF1 and ENO1 promoters, the Tn5 ble gene and the CYC1 terminator [24].
• Interestingly, deletion of FBP1 led to reduced sensitivity to MMS, but not to other DNA-damaging agents, such as 4-NQO or phleomycin [25].
• Finally, Xrs2 is phosphorylated after phleomycin treatment in a TEL1-dependent manner during S phase, whereas no significant Xrs2 phosphorylation is detected after MMS treatment [26].
• Here we describe an additional set of four completely heterologous loxP-flanked marker cassettes carrying the genes URA3 and LEU2 from Kluyveromyces lactis, his5(+) from Schizosaccharomyces pombe and the dominant resistance marker ble(r) from the bacterial transposon Tn5, which confers resistance to the antibiotic phleomycin [27].
• H7 parasites were complemented with BAG1 using phleomycin selection [28].

Analytical, diagnostic and therapeutic context of Phleomycin

• Crystallization and preliminary X-ray data of a phleomycin-binding protein from Streptoalloteichus hindustanus [29].
• Phleomycin resistance was stably transmitted to sexual offspring as a dominant nuclear trait as confirmed by Southern blotting [30].
• Bioassays were developed and used to compare the cytotoxicities of freshly dissolved bleomycin and phleomycin with the cytotoxicities of lysates prepared from bleomycin- and phleomycin-treated cells [31].
• An attempt has been made, by means of electron microscopy, to explain how phleomycin distributes early versus late wave cells, using a mercury substitution stain to detect the antibiotic [32].
• Transformation resulted in phleomycin resistant clones which were confirmed by PCR to contain the resistance cassette [33].

References