Site-specific cleavage of supercoiled DNA by ascorbate/Cu(II)

Wang, Yan Ming; Ness, Brian G. Van

doi:10.1093/nar/17.17.6915

Cited by 39 publications

(19 citation statements)

References 30 publications

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“…These cleavages might be directed by redox-reactive iron bound at specific ribosomal sites, for example, through interactions with rRNA or ribosomal proteins in the proximity of the RNA backbone. Previous studies have shown that binding of redox-active metals to target DNA and RNA molecules can give rise to oxidizing species that are not freely diffusible, thereby producing site-specific cleavages (33)(34)(35)(36). Studies have also shown that Fe 2+ can substitute for Mg 2+ in RNA (37), with highly structured RNA often exhibiting preferred sites for Fe 2+ binding (33).…”

Section: Iron-dependent Site-specific Cleavage Of 25s Rrna In Vitromentioning

confidence: 99%

Iron-dependent cleavage of ribosomal RNA during oxidative stress in the yeast Saccharomyces cerevisiae

Zinskie

Ghosh

Trainor

et al. 2018

Journal of Biological Chemistry

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Stress-induced strand breaks in rRNA have been observed in many organisms, but the mechanisms by which they originate are not well understood. Here, we show that a chemical rather than enzymatic mechanism initiates rRNA cleavages during oxidative stress in yeast (Saccharomyces cerevisiae). We used cells lacking the mitochondrial glutaredoxin Grx5 to demonstrate that oxidant-induced cleavage formation in 25S rRNA correlates with intracellular iron levels. Sequestering free iron by a chemical or genetic means decreased the extent of rRNA degradation and relieved the hypersensitivity of grx5 cells to the oxidants. Importantly, subjecting purified ribosomes to an in vitro iron/ascorbate reaction precisely recapitulated the 25S rRNA cleavage pattern observed in cells, indicating that redox activity of the ribosome-bound iron is responsible for the strand breaks in the rRNA. In summary, our findings provide evidence that oxidative stress-associated rRNA cleavages can occur through rRNA strand scission by redox-active, ribosomebound iron that potentially promotes Fenton reaction-induced hydroxyl radical production, implicating intracellular iron as a key determinant of the effects of oxidative stress on ribosomes. We propose that iron binding to specific ribosome elements primes rRNA for cleavages that may play a role in redox-sensitive tuning of the ribosome function in stressed cells.

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Section: Iron-dependent Site-specific Cleavage Of 25s Rrna In Vitromentioning

confidence: 99%

Iron-dependent cleavage of ribosomal RNA during oxidative stress in the yeast Saccharomyces cerevisiae

Zinskie

Ghosh

Trainor

et al. 2018

Journal of Biological Chemistry

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“…In an earlier study site-specific DNA cleavage by ascorbic acid in the presence of Cu(II) was described [21] . Using a cellular system of lymphocytes, we have shown that ascorbate (200 M ) in the presence of exogenously added 20 M cupric chloride (Cu(II)) gives a degree of DNA breakage which was considerably greater than that caused by ascorbate alone ( fig.…”

Section: Oxidative Dna Cleavage By Ascorbate In Vitro and In Human Lymentioning

confidence: 99%

Catalytic Therapy of Cancer by Ascorbic Acid Involves Redox Cycling of Exogenous/Endogenous Copper Ions and Generation of Reactive Oxygen Species

et al. 2010

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Catalytic therapy is a cancer treatment modality based on the generation of reactive oxygen species (ROS) through administration of ascorbate/medicinal herbal extracts and copper. It is known that antioxidants such as ascorbate also exhibit prooxidant activity in the presence of transition metals such as copper. Based on our work and that in the literature, in this review we propose a mechanism for the cytotoxic action of ascorbate against cancer cells. It involves redox cycling of exogenous/endogenous copper ions and the consequent generation of ROS leading to oxidative DNA breakage. Using human peripheral lymphocytes and the Comet assay, we have shown that ascorbic acid is able to cause oxidative breakage in cellular DNA. Such DNA degradation is inhibited by neocuproine (a Cu(I) sequestering agent) and scavengers of ROS indicating that the cellular DNA breakage involves the generation of Cu(I) and formation of ROS. Similar results are also obtained with plant polyphenol antioxidants that are important constituents of medicinal herbal extracts. Copper is an essential component of chromatin and can take part in redox reactions. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and ascorbate/plant polyphenols to generate ROS. In this review we cite evidence to indicate that in catalytic therapy cytotoxic action against cancer cells involves redox cycling of exogenous/endogenous copper ions.

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“…As shown in Figure 3(a), the temperature at about 244. 6 C was the onset temperature of decomposition for chitosan. 19 In Figure 3(b,c), Vitamin C showed the melting point at 196.83 C, which was decreased to 191.94 C in the chitosan-vitamin C mixture (2 : 1, g : g).…”

Section: Dsc Analysismentioning

confidence: 99%

“…The biochemical functions of VC, especially its functions in antivirus and antitumor are of increasing interests. 6 However, the use of VC is limited by its physical and chemical instability. VC is a six-carbon keto-lactone, which contains four hydroxyls and a lactone.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of chitosan‐vitamin C complexes

Tian

Wang

et al. 2009

J of Applied Polymer Sci

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Chitosan (CS) is a biocompatible, biodegradable, and nontoxic polysaccharide polymer. It dissolves in water only if the pH is lower than 6.5. To extend its range of application, many water-soluble derivatives have, therefore, been prepared. In this research, chitosanvitamin C complexes (CSVC) were synthesized and characterized with FTIR, DSC, and 1 H-NMR. The solubility of CSVC in distilled water was greatly improved. The O 2 -scavenging activity of CSVC was compared with CS and vitamin C (VC) by measuring the auto-oxidation rate of pyrogallic acid. Results showed that the scavenging activity on O 2 À by CSVC was stronger than that by CS.

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Site-specific cleavage of supercoiled DNA by ascorbate/Cu(II)

Cited by 39 publications

References 30 publications

Iron-dependent cleavage of ribosomal RNA during oxidative stress in the yeast Saccharomyces cerevisiae

Iron-dependent cleavage of ribosomal RNA during oxidative stress in the yeast Saccharomyces cerevisiae

Catalytic Therapy of Cancer by Ascorbic Acid Involves Redox Cycling of Exogenous/Endogenous Copper Ions and Generation of Reactive Oxygen Species

Synthesis and evaluation of chitosan‐vitamin C complexes

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