Magnesium binding and conformational change of DNA in chromatin

Watanabe, Kazutada; Iso, Koujiro

doi:10.1021/bi00302a007

Cited by 25 publications

(12 citation statements)

References 56 publications

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“…35 As with nonstochiometric DNA complexes, only 50% of DNA's charge in chromatin is neutralized by histones. 7,15 The effects described in the present study may model the effect of divalent cations on inducing the greater compaction of chromatin. 35 Histone tails contain a high proportion of charged residues and therefore resemble the synthetic polycations used in the present study.…”

Section: Discussionmentioning

confidence: 91%

“…The fraction of DNA charges neutralized by histones is close to 50%. 7,15 In this article, we offer a simple experimental model involving low molecular weight salts as key facilitators in the further condensation of nonstoichiometric DNA/polycation complexes. Such a model helps to explain some basic physico-chemical phenomena taking place during salt-induced modulation of chromatin assembly/disassembly.…”

Section: Introductionmentioning

confidence: 99%

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Condensation of nonstochiometric DNA/polycation complexes by divalent cations

2006

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This study found that divalent cations induced the further condensation of partially condensed DNA within nonstochiometric polycation complexes. The addition of a few mmol of a divalent cation such as calcium reduced by half the inflection point at which DNA became fully condensed by poly-L-lysine (PLL) and a variety of other polycations. The effect on DNA condensation was initially observed using a new method, which is based on the concentration-dependent self-quenching of fluorescent moieties (e.g., rhodamine) covalently linked to the DNA backbone at relatively high densities. Additional analyses, which employed ultracentrifugation, dynamic light scattering, agarose gel electrophoresis, and atomic force microscopy, confirmed the effect of divalent cations. These results provide an additional accounting of the process by which divalent cations induce greater chromatin compaction that is based on the representation of chromatin fibers as a nonstoichiometric polyelectrolyte complex. They also offer a new approach to assemble nonviral vectors for gene therapy.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Condensation of nonstochiometric DNA/polycation complexes by divalent cations

2006

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“…On the other hand the tendency of Mg2+ to bind to DNA is well documented (17,18). The simplest way for the metal ion to generate a ternary complex would be to form a bridge between the quinolone moiety and the nucleic acid.…”

Section: Resultsmentioning

confidence: 99%

“…The (17,18). Since from the above equilibria it follows that K1K3 = K2K4, K3 can be evaluated to be =4.2 x 104 M-1.…”

Section: Resultsmentioning

confidence: 99%

Quinolone binding to DNA is mediated by magnesium ions.

Palù

Valisena

Ciarrocchi

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

163

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The binding of plasmid DNA to norfloxacin, a quinolone antibacterial agent, was investigated by fluorescence, electrophoretic DNA unwinding, and affinity chromatography techniques. The amount of quinolone bound to DNA was modulated by the concentration of Mg2+. No interaction was evident in the absence of Mg2+ or in the presence of an excess of Mg2+, whereas maximum binding was observed at a Mg2+ concentration of 1-2 mM. The experimental data can be fitted to the formation of three types of Mg adducts: a binary adduct with norfloxacin and Mg2+, a binary adduct with DNA and Mg2+, and a ternary adduct with quinolone, plasmid, and Mg2+. We propose a model for the ternary complex, in which Mg acts as a bridge between the phosphate groups of the nucleic acid and the carbonyl and carboxyl moieties of norfloxacin. Additional stabilization may arise from stacking interactions between the condensed rings of the drug and DNA bases (especially guanine and adenine), which may account for the preference exhibited by quinolones for single-stranded and purine-rich regions ofnucleic acids. Other possible biochemical pathways of drug action are suggested by the observation that norfloxacin binds Mg2+ under conditions that are close to physiological.Conflicting literature reports have been accumulating on the role played by DNA in the mechanism of action of quinolone compounds. Although a large amount of biological data has indicated that DNA gyrase was the target for quinolone compounds (1-4), recent reports dismissed DNA gyrase as the target and pointed to DNA as the direct binding species (5). In fact, a cooperative interaction was proposed to occur between quinolones and supercoiled DNA. Subsequent publications by the same laboratory have modified this view extensively (6-8). In particular, Shen et al. (7) have proposed that in the presence of ATP bound gyrase induces a specific quinolone binding site in the relaxed DNA substrate. Gelelectrophoresis experiments by Tornaletti and Pedrini (9) showed that norfloxacin (Nor) is able to unwind the DNA double helix in the presence of Mg2+. On the other hand 19F NMR measurements failed to show any direct DNAquinolone interaction (10). We were also unable to detect binding using fluorescence spectroscopy techniques (11).Even if reconsidered in terms of affinity, the interaction with DNA is still of great concern because of the possible long-term genotoxicity of quinolone compounds, which are increasingly adopted as first-choice antibiotics for the treatment of many infections, and because it addresses the real mechanism of action of this class of molecules. To shed some light on this cumbersome problem, we have focused our attention on the role of Mg2+ in the binding of the model quinolone drug Nor to plasmid DNA. Our approach includes fluorescence and affinity chromatography measurements and electrophoretic DNA-unwinding assays. MATERIALS AND METHODSChemicals. Nor and [14C]Nor (specific activity, 46.5 ,uCi/ mg; 1 Ci = 37 GBq) were a kind gift of Merck Sharp & Dohme. Magnesium...

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“…The adminis tration of estradiol inhibited this depression. The mechanisms are unclear, but it is well known that during Mg-depletion in diet the protein synthesis was depressed or modified (30)(31)(32)(33) and that the administration of estrogen induced some enzymes (34,35).…”

Section: Discussionmentioning

confidence: 99%

Sex Difference of Pinnal Hyperemia in Magnesium-Deficient Rats: Effects of Castration and Administration of Sex Hormone

Nishio

Miyazaki

Ishiguro

et al. 1986

Japanese Journal of Pharmacology

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Abstract-In the course of studies on the effects of magnesium (Mg) depletion in the diet (0.001% Mg) on mature rats (10 week-old), it became apparent that females developed less hyperemia than males.In the females, the time of onset and severity of hyperemia were enhanced by castration, but not in the males. These data suggest that the development of hyperemia in Mg-deficient adult rats depends on the female sex hormone. The effects of administration of estradiol were examined, using immature rats (3 week-old), in relation to hyperemia and histamine metabolism.Two to 3 days after feeding young male and female rats a Mg-deficient diet, the pinnal hyperemia appeared in the same degree.The hyperemia was reduced by the administration of estradiol benzoate (0.04-0.08 mg/100 g body wt. per day, s.c.) every day. The increments in urinary histamine excretion, splenic histamine content and histidine decarboxylase activity during Mg-deficiency were markedly reduced by the administration of estradiol. The sex difference in the hyperemia which appeared upon Mg-depletion depends on the effects of the female hormone, estradiol, on histamine metabolism.

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Magnesium binding and conformational change of DNA in chromatin

Cited by 25 publications

References 56 publications

Condensation of nonstochiometric DNA/polycation complexes by divalent cations

Condensation of nonstochiometric DNA/polycation complexes by divalent cations

Quinolone binding to DNA is mediated by magnesium ions.

Sex Difference of Pinnal Hyperemia in Magnesium-Deficient Rats: Effects of Castration and Administration of Sex Hormone

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