A new approach to DNA bending by polyamines and its implication in DNA condensation

Pastré, David; Piétrement, Olivier; Landousy, Fabrice; Hamon, Loïc; Sorel, Isabelle; David, M; Delain, Etienne; Zozime, A.; Cam, Eric Le

doi:10.1007/s00249-005-0025-7

Cited by 25 publications

(17 citation statements)

References 52 publications

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“…Noncovalent association with DNA is not uniquely an attribute of intercalators, but it also applies to agents that associate externally with the DNA grooves [Feuerstein et al, 1986;Smoluk et al, 1988;Strekowski et al, 1989;Pastré et al, 2006]. Such agents can have either antigenotoxic or enhancing effects depending on physiological conditions .…”

Section: Discussionmentioning

confidence: 97%

Potentiation of the mutagenicity and recombinagenicity of bleomycin in yeast by unconventional intercalating agents

Hoffmann

Laterza

Sylvia

et al. 2011

Environ and Mol Mutagen

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Interactions between bleomycin (BLM) and conventional or unconventional intercalating agents were analyzed in an assay for mitotic gene conversion at the trp5 locus and reversion of the ilv1-92 allele in Saccharomyces cerevisiae strain D7. BLM is a potent recombinagen and mutagen in the assay. Various chemicals modulate the genetic activity of BLM, producing either antimutagenic effects or enhanced genotoxicity. Effects of cationic amino compounds include enhancement of BLM activity by aminoacridines and protection against BLM by aliphatic amines. The potentiation of BLM is similar to findings in a micronucleus-based BLM amplification assay in Chinese hamster V79 cells. In this study, the amplification of BLM activity was explored in yeast using known intercalators, compounds structurally related to known intercalators, and unconventional intercalators that were identified on the basis of computer modeling or results in the Chinese hamster BLM amplification assay. As shown in previous studies, the classical intercalator 9-aminoacridine (9AA) caused dose-dependent enhancement of BLM activity. Other compounds found to enhance the induction of mitotic recombination and point mutations in strain D7 were chlorpromazine, chloroquine, mefloquine, tamoxifen, diphenhydramine, benzophenone, and 3-hydroxybenzophenone. The increased activity was detectable by cotreatment of yeast with BLM and the modulator compound in growth medium or by separate interaction of the intercalator with DNA followed by BLM treatment of nongrowing cells in buffer. The data support the interpretation drawn from micronucleus assays in mammalian cells that BLM enhancement results from DNA intercalation and may be useful in detecting noncovalent interactions with DNA. Environ.

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Section: Discussionmentioning

confidence: 97%

Potentiation of the mutagenicity and recombinagenicity of bleomycin in yeast by unconventional intercalating agents

Hoffmann

Laterza

Sylvia

et al. 2011

Environ and Mol Mutagen

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“…A substantial number of publications implicate polyamines to affect the topology of DNA; specifically, polyamines can alter DNA bending (31,68), as well as promote the B-DNA structure to both A-DNA and Z-DNA transitions (32,80), and affect topoisomerase function (46), for example.…”

Section: Vol 191 2009mentioning

confidence: 99%

“…In terms of the mechanism as to how spermidine affects the expression of the PrrA-regulated genes described here, two earlier lines of evidence describing (i) the strong effects of polyamines on DNA topology (31,32,46,68,80) and (ii) earlier suggestions about possible effects of DNA topology on PrrA-regulated gene expression (29,48,53,71,90) prompted us to test whether the observed effects of spermidine reported here might be due, at least in part, to changes in the topology of the DNA regulatory region promoted by the polyamine. We report that the expression of transcriptional lacZ fusions to the RSP3361 gene, as well as pucB (RSP0314 gene), is stimulated by negative supercoils, in vivo and in the absence of spermidine, as shown using transcriptionally driven topological alteration (TDTA) with a divergently transcribed wild-type (WT) (P) and mutant (P down ) promoter to the RSP3361 gene regulatory region.…”

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confidence: 94%

“…Because of previously reported effects of polyamines on DNA topology (31,32,46,68,80) and earlier suggestions about the possible effects of DNA topology on PrrA-regulated gene expression (29,48,53,71,90), we chose to test the possible effects of DNA supercoiling on expression of the RSP3361 gene. DNA supercoiling has well-known generalized effects on gene expression (70) and on photosynthesis genes, which are mostly PrrA regulated, in particular (53).…”

mentioning

confidence: 99%

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Regulation of Gene Expression by PrrA in Rhodobacter sphaeroides 2.4.1: Role of Polyamines and DNA Topology

Eraso

Kaplan

2009

J Bacteriol

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In the present study, we show in vitro binding of PrrA, a global regulator in Rhodobacter sphaeroides 2.4.1, to the PrrA site 2, within the RSP3361 locus. Specific binding, as shown by competition experiments, requires the phosphorylation of PrrA. The binding affinity of PrrA for site 2 was found to increase 4-to 10-fold when spermidine was added to the binding reaction. The presence of extracellular concentrations of spermidine in growing cultures of R. sphaeroides gave rise to a twofold increase in the expression of the photosynthesis genes pucB and pufB, as well as the RSP3361 gene, under aerobic growth conditions, as shown by the use of lacZ transcriptional fusions, and led to the production of light-harvesting spectral complexes. In addition, we show that negative supercoiling positively regulates the expression of the RSP3361 gene, as well as pucB. We show the importance of supercoiling through an evaluation of the regulation of gene expression in situ by supercoiling, in the case of the former gene, as well as using the DNA gyrase inhibitor novobiocin. We propose that polyamines and DNA supercoiling act synergistically to regulate expression of the RSP3361 gene, partly by affecting the affinity of PrrA binding to the PrrA site 2 within the RSP3361 gene.

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“…Depending on the pH value in the environments, polyamines can be highly positively charged molecules and potent nucleophiles. Through charge interactions, these compounds can cause DNA condensation in vitro (18), and as nucleophiles they are able to form covalent adducts with ␤-lactams (29) and potentially with other signal compounds or protein targets. To avoid these potential lethal effects, the cells need to maintain polyamine homeostasis through coordinated regulation on biosynthesis, catabolism, and uptake.…”

mentioning

confidence: 99%

γ-Glutamyl Spermine Synthetase PauA2 as a Potential Target of Antibiotic Development against Pseudomonas aeruginosa

Yao

Zhang

et al. 2012

Antimicrob Agents Chemother

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cPolyamines are absolute requirements for cell growth. When in excess, Pseudomonas aeruginosa possesses six ␥-glutamylpolyamine synthetases (GPSs) encoded by the pauA1-pauA7 genes to initiate polyamine catabolism. Recently, the pauA2 mutant was reported to lose the capability to grow on spermine (Spm) and spermidine (Spd) as sole carbon and nitrogen sources. Although this mutant grew normally in defined minimal medium and LB broth, growth was completely abolished by the addition of Spm or Spd. These two compounds exert a bactericidal effect (Spm > Spd) on the mutants as demonstrated by MIC measurements (over 500-fold reduction) and time-killing curves. Spm toxicity in the pauA2 mutant was attenuated when the major uptake system was further deleted from the strain, suggesting cytoplasmic targets of toxicity. In addition, the synergistic effect of Spm and carbenicillin in the wild-type strain PAO1 was diminished in mutants without functional PauA2. Furthermore, Spm MIC was reduced by 8-fold when the Spm uptake system was deleted from the wild-type strain, suggesting a second target of Spm toxicity in the periplasm. Experiments were also conducted to test the hypothesis that native Spm and Spd in human serum may be sufficient to kill the pauA2 mutant. Growth of the mutant was completely inhibited by 40% (vol/vol) human serum, whereas the parental strain required 80%. Colony counts indicated that the mutant but not the parent was in fact killed by human plasma. In addition, carbenicillin MIC against the mutant was reduced by 16-fold in the presence of 20% human serum while that of the parental strain remained unchanged. Taking PauA2 as the template, sequence comparison indicates that putative PauA2 homologues are widespread in a variety of Gram-negative bacteria. In summary, this study reveals the importance of GPS in alleviation of polyamine toxicity when in excess, and it provides strong support to the feasibility of GPS as a molecular target for new antibiotic development.

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A new approach to DNA bending by polyamines and its implication in DNA condensation

Cited by 25 publications

References 52 publications

Potentiation of the mutagenicity and recombinagenicity of bleomycin in yeast by unconventional intercalating agents

Potentiation of the mutagenicity and recombinagenicity of bleomycin in yeast by unconventional intercalating agents

Regulation of Gene Expression by PrrA in Rhodobacter sphaeroides 2.4.1: Role of Polyamines and DNA Topology

γ-Glutamyl Spermine Synthetase PauA2 as a Potential Target of Antibiotic Development against Pseudomonas aeruginosa

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