The Experts below are selected from a list of 75219 Experts worldwide ranked by ideXlab platform
Paraic M Keane - One of the best experts on this subject based on the ideXlab platform.
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monitoring Guanine photo oxidation by enantiomerically resolved ru ii dipyridophenazine complexes using inosine substituted oligonucleotides
2015Co-Authors: James P Hall, Paraic M Keane, Fergus E Poynton, Susan J Quinn, Igor V Sazanovich, Ian P Clark, Michael Towrie, Thorfinnur Gunnlaugsson, Christine J. CardinAbstract:The intercalating [Ru(TAP)2(dppz)]2+ complex can photo-oxidise Guanine in DNA, although in mixed-sequence DNA it can be difficult to understand the precise mechanism due to uncertainties in where and how the complex is bound. Replacement of Guanine with the less oxidisable inosine (I) base can be used to understand the mechanism of electron transfer (ET). Here the ET has been compared for both Λ- and Δ-enantiomers of [Ru(TAP)2(dppz)]2+ in a set of sequences where Guanines in the readily oxidisable GG step in {TCGGCGCCGA}2 have been replaced with I. The ET has been monitored using picosecond and nanosecond transient absorption and picosecond time-resolved IR spectroscopy. In both cases inosine replacement leads to a diminished yield, but the trends are strikingly different for Λ- and Δ-complexes.
Christine J. Cardin - One of the best experts on this subject based on the ideXlab platform.
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monitoring Guanine photo oxidation by enantiomerically resolved ru ii dipyridophenazine complexes using inosine substituted oligonucleotides
2015Co-Authors: James P Hall, Paraic M Keane, Fergus E Poynton, Susan J Quinn, Igor V Sazanovich, Ian P Clark, Michael Towrie, Thorfinnur Gunnlaugsson, Christine J. CardinAbstract:The intercalating [Ru(TAP)2(dppz)]2+ complex can photo-oxidise Guanine in DNA, although in mixed-sequence DNA it can be difficult to understand the precise mechanism due to uncertainties in where and how the complex is bound. Replacement of Guanine with the less oxidisable inosine (I) base can be used to understand the mechanism of electron transfer (ET). Here the ET has been compared for both Λ- and Δ-enantiomers of [Ru(TAP)2(dppz)]2+ in a set of sequences where Guanines in the readily oxidisable GG step in {TCGGCGCCGA}2 have been replaced with I. The ET has been monitored using picosecond and nanosecond transient absorption and picosecond time-resolved IR spectroscopy. In both cases inosine replacement leads to a diminished yield, but the trends are strikingly different for Λ- and Δ-complexes.
Stephen R Lloyd - One of the best experts on this subject based on the ideXlab platform.
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efficient and error free replication past a minor groove n2 Guanine adduct by the sequential action of yeast rev1 and dna polymerase ζ
2004Co-Authors: Todd M Washington, Irina G Minko, Stephen R Lloyd, Lajos Haracska, Thomas M. Harris, R.e. JohnsonAbstract:Rev1, a member of the Y family of DNA polymerases, functions in lesion bypass together with DNA polymerase ζ (Polζ). Rev1 is a highly specialized enzyme in that it incorporates only a C opposite template G. While Rev1 plays an indispensable structural role in Polζ-dependent lesion bypass, the role of its DNA synthetic activity in lesion bypass has remained unclear. Since interactions of DNA polymerases with the DNA minor groove contribute to the nearly equivalent efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases, here we examine the possibility that unlike other DNA polymerases, Rev1 does not come into close contact with the minor groove of the incipient base pair, and that enables it to incorporate a C opposite the N2-adducted Guanines in DNA. To test this idea, we examined whether Rev1 could incorporate a C opposite the γ-hydroxy-1,N2-propano-2′deoxyguanosine DNA minor-groove adduct, which is formed from the reaction of acrolein with the N2 of Guanine. Acrolein, an α,β-unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from other oxidation reactions. We show here that Rev1 efficiently incorporates a C opposite this adduct from which Polζ subsequently extends, thereby completing the lesion bypass reaction. Based upon these observations, we suggest that an important role of the Rev1 DNA synthetic activity in lesion bypass is to incorporate a C opposite the various N2-Guanine DNA minor-groove adducts that form in DNA.
Lawrence P. Wackett - One of the best experts on this subject based on the ideXlab platform.
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Bacterial Ammeline Metabolism via Guanine Deaminase
2009Co-Authors: Jennifer L. Seffernick, Anthony G. Dodge, Michael J. Sadowsky, John A. Bumpus, Lawrence P. WackettAbstract:Melamine toxicity in mammals has been attributed to the blockage of kidney tubules by insoluble complexes of melamine with cyanuric acid or uric acid. Bacteria metabolize melamine via three consecutive deamination reactions to generate cyanuric acid. The second deamination reaction, in which ammeline is the substrate, is common to many bacteria, but the genes and enzymes responsible have not been previously identified. Here, we combined bioinformatics and experimental data to identify Guanine deaminase as the enzyme responsible for this biotransformation. The ammeline degradation phenotype was demonstrated in wild-type Escherichia coli and Pseudomonas strains, including E. coli K12 and Pseudomonas putida KT2440. Bioinformatics analysis of these and other genomes led to the hypothesis that the ammeline deaminating enzyme was Guanine deaminase. An E. coli Guanine deaminase deletion mutant was deficient in ammeline deaminase activity, supporting the role of Guanine deaminase in this reaction. Two Guanine deaminases from disparate sources (Bradyrhizobium japonicum USDA 110 and Homo sapiens) that had available X-ray structures were purified to homogeneity and shown to catalyze ammeline deamination at rates sufficient to support bacterial growth on ammeline as a sole nitrogen source. In silico models of Guanine deaminase active sites showed that ammeline could bind to Guanine deaminase in a similar orientation to Guanine, with a favorable docking score. Other members of the amidohydrolase superfamily that are not Guanine deaminases were assayed in vitro, and none had substantial ammeline deaminase activity. The present study indicated that widespread Guanine deaminases have a promiscuous activity allowing them to catalyze a key reaction in the bacterial transformation of melamine to cyanuric acid and potentially contribute to the toxicity of melamine.
Bernd Giese - One of the best experts on this subject based on the ideXlab platform.
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Long-distance charge transport through DNA. An extended hopping model*
2015Co-Authors: Bernd Giese, Martin Spichty, Stefan WesselyAbstract:Abstract: Long-distance transfer of a positive charge through DNA can be described by a hopping model. In double strands where the (A:T)n bridges between the Guanines are short (n ≥ 3), the charge hops only between Guanines, and each hopping step depends strongly upon the Guanine to Guanine distances. In strands where the (A:T)n sequences between the Guanines are rather long (n ≥ 4), also the adenines act as charge carriers. To predict the yields of the H2O-trapping products one has to take into account not only the charge-transfer rates but also the rates of H2O-trapping reactions. In the 1990s, the question of long-distance electron transfer through DNA raised a controversial dis-cussion [1]. We entered this area three years ago by studying radical-induced DNA strand cleavage reac-tions. Our experiments showed that photolysis of a 4'-acylated nucleoside in the DNA double strand 1 yields radical cation 2 that selectively oxidizes Guanine (G) and forms a Guanine radical cation (G•+) in 3 (Fig. 1) [2]. This reaction sequence led to an assay that made it possible to follow the charge migration through DNA by trapping of the positive charge at the heterocyclic base [3]. In order to understand the experimental results, we suggested in 1998 a hopping mechanism [3] for long-distance charge transport through DNA, which is based on the theoretical model of Jortner [4]. A similar hopping mechanism, which is slightly different in the details, was also suggested by Schuster [5], and today there is a con
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direct observation of hole transfer through dna by hopping between adenine bases and by tunnelling
2001Co-Authors: Bernd Giese, Jerome Amaudrut, Annekathrin Kohler, Martin Spormann, Stephan WesselyAbstract:The function of DNA during oxidative stress1 and its suitability as a potential building block for molecular devices2,3,4 depend on long-distance transfer of electrons and holes through the molecule, yet many conflicting measurements of the efficiency of this process have been reported5,6. It is accepted that charges are transported over long distances through a multistep hopping reaction7,8,9,10,11; this ‘G-hopping’8 involves positive charges moving between Guanines (Gs), the DNA bases with the lowest ionization potential. But the mechanism fails to explain the persistence of efficient charge transfer when the Guanine sites are distant7,12, where transfer rates do not, as expected, decrease rapidly with transfer distance. Here we show experimentally that the rate of charge transfer between two Guanine bases decreases with increasing separation only if the Guanines are separated by no more than three base pairs; if more bridging base pairs are present, the transfer rates exhibit only a weak distance dependence. We attribute this distinct change in the distance dependence of the rate of charge transfer through DNA to a shift from coherent superexchange charge transfer (tunnelling) at short distances to a process mediated by thermally induced hopping of charges between adenine bases (A-hopping) at long distances. Our results confirm theoretical predictions of this behaviour13,14,15,16,17, emphasizing that seemingly contradictory observations of a strong8,9 as well as a weak7,12 influence of distance on DNA charge transfer are readily explained by a change in the transfer mechanism.
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Long-distance charge transport through DNA. An extended hopping model
2001Co-Authors: Bernd Giese, Martin Spichty, Stefan WesselyAbstract:Long-distance transfer of a positive charge through DNA can be described by a hopping model. In double strands where the (A:T) n bridges between the Guanines are short (n ≥ 3), the charge hops only between Guanines, and each hopping step depends strongly upon the Guanine to Guanine distances. In strands where the (A:T) n sequences between the Guanines are rather long (n ≥ 4), also the adenines act as charge carriers. To predict the yields of the H2O-trapping products one has to take into account not only the charge-transfer rates but also the rates of H 2O-trapping reactions.
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long distance charge transport through dna quantification and extension of the hopping model
2000Co-Authors: Bernd Giese, Martin SpichtyAbstract:Long distance charge transport through DNA occurs by a hopping mechanism. If the positive charge is injected into a Guanine base, all Guanines act as charge carriers. Because of the strong influence that the distance has on the charge-transfer step, DNA strands with long adenine:thymine sequences also involve adenine as charge carriers. A prerequsite for this mechanism is that the electron transfer to an adjacent adenine base is faster than the H2O trapping reaction of the Guanine radical cation. We have developed a model that can explain and qualitatively predict the product yields.
