Oxidative Damage to DNA Constituents by Iron-mediated Fenton Reactions

Luo, Yongzhang; Henle, Ernst S.; Linn, Stuart

doi:10.1074/jbc.271.35.21167

Cited by 150 publications

(96 citation statements)

References 36 publications

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“…In contrast, our laboratory found that nucleoside damage following exposure of DNA to Fe 2ϩ and H 2 O 2 was not equally distributed among the nucleosides (25). Since we have proposed that DNA damage in 0.5 mM H 2 O 2 was caused by Fe 2ϩ ions that associate differently with DNA than those which cause damage at 50 mM H 2 O 2 , we have now investigated whether strand breaks vary in sequence location at the two H 2 O 2 concentrations.…”

mentioning

confidence: 52%

Sequence-specific DNA Cleavage by Fe2+-mediated Fenton Reactions Has Possible Biological Implications

Henle

Han

Tang

et al. 1999

Journal of Biological Chemistry

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316

228

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Preferential cleavage sites have been determined for Fe 2؉ /H 2 O 2 -mediated oxidations of DNA. In 50 mM H 2 O 2 , preferential cleavages occurred at the nucleoside 5 to each of the dG moieties in the sequence RGGG, a sequence found in a majority of telomere repeats. Within a plasmid containing a (TTAGGG) 81 human telomere insert, 7-fold more strand breakage occurred in the restriction fragment with the insert than in a similar-sized control fragment. This result implies that telomeric DNA could protect coding DNA from oxidative damage and might also link oxidative damage and iron load to telomere shortening and aging. In micromolar H 2 O 2 , preferential cleavage occurred at the thymidine within the sequence RTGR, a sequence frequently found to be required in promoters for normal responses of many procaryotic and eucaryotic genes to iron or oxygen stress. Computer modeling of the interaction of Fe 2؉ with RTGR in B-DNA suggests that due to steric hindrance with the thymine methyl, Fe 2؉ associates in a specific manner with the thymine flipped out from the base stack so as to allow an octahedrally-oriented coordination of the Fe 2؉ with the three purine N 7 residues. Fe 2؉ -dependent changes in NMR spectra of duplex oligonucleotides containing ATGA versus those containing AUGA or A 5m CGA were consistent with this model.

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mentioning

confidence: 52%

Sequence-specific DNA Cleavage by Fe2+-mediated Fenton Reactions Has Possible Biological Implications

Henle

Han

Tang

et al. 1999

Journal of Biological Chemistry

Self Cite

316

228

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“…100 lM Fe 2+ was high enough to produce sufficient number of DNA double-strand damages, but low enough not to cause significant decline in AFM image quality. 2 mM H 2 O 2 was used in the experiments since this concentration was biologically more relevant, as discussed in the literature [27].…”

Section: Dependence Of Dna Damage On Fe 2+ Concentrationmentioning

confidence: 99%

Quantitative measurement of hydroxyl radical induced DNA double‐strand breaks and the effect of N‐acetyl‐l‐cysteine

Yang

2006

FEBS Letters

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Reactive oxygen species, such as hydroxyl or superoxide radicals, can be generated by exogenous agents as well as from normal cellular metabolism. Those radicals are known to induce various lesions in DNA, including strand breaks and base modifications. These lesions have been implicated in a variety of diseases such as cancer, arteriosclerosis, arthritis, neurodegenerative disorders and others. To assess these oxidative DNA damages and to evaluate the effects of the antioxidant N-acetyl-L L-cysteine (NAC), atomic force microscopy (AFM) was used to image DNA molecules exposed to hydroxyl radicals generated via Fenton chemistry. AFM images showed that the circular DNA molecules became linear after incubation with hydroxyl radicals, indicating the development of double-strand breaks. The occurrence of the double-strand breaks was found to depend on the concentration of the hydroxyl radicals and the duration of the reaction. Under the conditions of the experiments, NAC was found to exacerbate the free radical-induced DNA damage.

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“…SCO2368 is also potentially a member of the sigma R regulon, since the consensus motif GGGAA(N18-20)C GTT, which is related to the sigma R binding site, was found in its promoter region (53). Proteins of this family might be involved in the limitation of growth under high oxidative stress in order to minimize mutagenic events occurring under these conditions (54). The ppk mutant is known to grow at a rate similar to that of the wt strain (13), and the lower expression of this protein in the ppk mutant at 96 h is difficult to interpret.…”

Section: Proteomic Studiesmentioning

confidence: 99%

Comparative Proteomic Analysis of Streptomyces lividans Wild-Type andppkMutant Strains Reveals the Importance of Storage Lipids for Antibiotic Biosynthesis

Maréchal

Decottignies

Marchand

et al. 2013

Appl Environ Microbiol

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dStreptomyces lividans TK24 is a strain that naturally produces antibiotics at low levels, but dramatic overproduction of antibiotics occurs upon interruption of the ppk gene. However, the role of the Ppk enzyme in relation to the regulation of antibiotic biosynthesis remains poorly understood. In order to gain a better understanding of the phenotype of the ppk mutant, the proteomes of the wild-type (wt) and ppk mutant strains, grown for 96 h on R2YE medium limited in phosphate, were analyzed. Intracellular proteins were separated on two-dimensional (2D) gels, spots were quantified, and those showing a 3-fold variation or more were identified by mass spectrometry. The expression of 12 proteins increased and that of 29 decreased in the ppk mutant strain. Our results suggested that storage lipid degradation rather than hexose catabolism was taking place in the mutant. In order to validate this hypothesis, the triacylglycerol contents of the wt and ppk mutant strains of S. lividans as well as that of Streptomyces coelicolor M145, a strain that produces antibiotics at high levels and is closely related to S. lividans, were assessed using electron microscopy and thin-layer chromatography. These studies highlighted the large difference in triacylglycerol contents of the three strains and confirmed the hypothetical link between storage lipid metabolism and antibiotic biosynthesis in Streptomyces.

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Oxidative Damage to DNA Constituents by Iron-mediated Fenton Reactions

Cited by 150 publications

References 36 publications

Sequence-specific DNA Cleavage by Fe2+-mediated Fenton Reactions Has Possible Biological Implications

Sequence-specific DNA Cleavage by Fe2+-mediated Fenton Reactions Has Possible Biological Implications

Quantitative measurement of hydroxyl radical induced DNA double‐strand breaks and the effect of N‐acetyl‐l‐cysteine

Comparative Proteomic Analysis of Streptomyces lividans Wild-Type andppkMutant Strains Reveals the Importance of Storage Lipids for Antibiotic Biosynthesis

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