Cleavage of DNA by Irradiation of Substituted Anthraquinones:  Intercalation Promotes Electron Transfer and Efficient Reaction at GG Steps

Ly, Danith H.; Kan, Yongzhi; Armitage, Bruce A.; Schuster, Gary B.

doi:10.1021/ja9615785

Cited by 173 publications

(188 citation statements)

References 23 publications

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“…In early experiments it was shown that photoexcitation of DNA in its normal B-type double helical form by intense nano-or picosecond 266 nm laser pulses induces a greater damage of guanines positioned on the 5′-side of purine bases, especially adjacent to guanine, than on guanines adjacent to pyrimidines. 7 This selectivity of G oxidation in different sequence context has been also observed employing one-electron oxidants generated by photosensitization of metal complexes, 3,8 anthraquinones, 4,9 naphthalimides, 10 riboflavin (RF), 11,12 4′-pivaloyl derivatives, 13,14 cyanobenzoyl and cyanobenzophenone substituted 2′-deoxyuridine 15,16 and other chemical one-electron oxidants. 17, 18 Saito and co-workers have shown that the enhancement of oxidative guanine damage increases with the number of contiguous guanines according to 5′-G < 5′-GG < 5′-GGG and that this phenomenon is correlated with the calculated gas phase ionization potentials (IP) for guanines in different sequence contexts.…”

Section: Introductionmentioning

confidence: 71%

Oxidation of Guanine in G, GG, and GGG Sequence Contexts by Aromatic Pyrenyl Radical Cations and Carbonate Radical Anions: Relationship between Kinetics and Distribution of Alkali-Labile Lesions

et al. 2008

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Oxidatively generated DNA damage induced by the aromatic radical cation of the pyrene derivative 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene (BPT), and by carbonate radicals anions, was monitored from the initial one-electron transfer, or hole injection step, to the formation of hot alkali-labile chemical end-products monitored by gel electrophoresis. The fractions of BPT molecules bound to double-stranded 20-35-mer oligonucleotdes with noncontiguous guanines G, and grouped as contiguous GG and GGG sequences, were determined by a fluorescence quenching method. Utilizing intense nanosecond 355 nm Nd: Yag laser pulses, the DNA-bound BPT molecules were photoionized to BPT •+ radicals by a consecutive two-photon ionization mechanism. The BPT •+ radicals thus generated within the duplexes selectively oxidize guanine by intraduplex electron transfer reactions, and the rate constants of these reactions follow the trend 5′-..GGG.. > 5′-..GG.. > 5′-..G… In the case of CO 3 •− radicals, the oxidation of guanine occurs by intermolecular collision pathways and the bimolecular rate constants are independent of base sequence context. However, the distributions of the end-products generated by CO 3 •− radicals, as well as by BPT •+ , is base sequence context-dependent and is greater than in isolated guanines at the 5′-G in 5′-…GG… sequences, and the first two 5′-guanines in the 5′-..GGG sequences. These results help to clarify the conditions that lead to a similar or different base sequence dependence of the initial hole injection step and the final distribution of oxidized, alkalilabile guanine products. In the case of the intermolecular one-electron oxidant CO 3 •− , the rate constant of hole injection is similar for contiguous and isolated guanines, but the subsequent equilibration of holes by hopping favors trapping and product formation at contiguous guanines, and the sequence dependence of these two phenomena are not correlated. In contrast, in the case of the DNA bound oxidant BPT •+ , the hole injection rate constants, as well as hole equilibration, exhibit a similar dependence on base sequence context, and are thus correlated to one another.

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Section: Introductionmentioning

confidence: 71%

Oxidation of Guanine in G, GG, and GGG Sequence Contexts by Aromatic Pyrenyl Radical Cations and Carbonate Radical Anions: Relationship between Kinetics and Distribution of Alkali-Labile Lesions

et al. 2008

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“…Intensive investigation has shown that irradiation of a DNA sample that contains a covalently linked AQ group at 350 nm, at which only the AQ absorbs, forms the excited singlet state of the AQ, which rapidly intersystem crosses to form its triplet state (21,22). The triplet is a powerful one-electron oxidant that initiates electron transfer from an adjacent nucleobase to form the AQ radical anion and a base radical cation (23)(24)(25). The AQ radical anion is consumed by reaction with O 2 to form superoxide, and the base radical cation can migrate through the DNA by hopping until it is trapped (usually at a guanine) by reaction with H 2 O and͞or O 2 (26,27).…”

Section: Resultsmentioning

confidence: 99%

Effect of condensate formation on long-distance radical cation migration in DNA

Das

Schuster

2005

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

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Long-distance radical cation transport was studied in DNA condensates. Linearized pUC19 plasmid was ligated to an oligomer containing a covalently linked anthraquinone group and six regularly spaced GG steps, which serve as traps for the migrating radical cation. Treatment of the linear, ligated plasmid with spermidine results in formation of condensates that were detected by light scattering and observed by transmission electron microscopy. Irradiation of the anthraquinone group in the condensate causes long-distance charge migration, which is detected by reaction at the remote guanines. The efficiency of charge migration in the condensate is significantly less than it is for the corresponding oligomer in solution. This result is attributed to a lower mobility for the migrating radical cation in the condensate, which is caused by inhibited formation of charge-transfer-effective states.charge transfer ͉ oxidative damage I t is well known that DNA is damaged by reactive chemical species. Extensive studies have shown that the one-electron oxidation of an oligonucleotide in solution creates a nucleobase radical cation (electron ''hole'') that may migrate hundreds of angstroms through duplex DNA before it is irreversibly trapped by reaction with H 2 O or O 2 (1-3). Trapping occurs most commonly at a guanine, because it is the base with the lowest ionization potential (4), and this reaction leads to mutagenic products such as 8-oxoguanine (5-8). DNA within cells is tightly packed and does not closely resemble oligonucleotides in solution. An examination of radical-cation hopping through DNA in loosely organized nucleosome core particles showed that histone binding does not affect the pattern and extent of oxidation (9). However, it is not known how the long-distance radical-cation migration that is observed in oligonucleotides is affected by conversion of the DNA to a well ordered structure. We began the systematic investigation of this question by examining the reactions of radical cations that were specifically introduced into DNA condensates.Multivalent cations like spermine or spermidine and proteins such as polylysine initiate DNA condensation (10-14). DNA condensates are nanometer-scale particles formed by the collapse of extended DNA chains into compact, ordered structures containing a small number of molecules (15, 16). These structures are recognized as models that are useful for studying gene packing in viruses, bacteria, and eukaryotic cells (17).We prepared condensates formed from the linearized pUC19 plasmid (which contains 2,686 bp) that had been ligated to an oligonucleotide containing a covalently linked anthraquinone (AQ) group (for photoinitiated introduction of a radical cation) and a series of regularly spaced GG steps (as traps for the radical cation) (Fig. 1) (18). Dynamic light-scattering results and examination by transmission electron microscopy (TEM) shows that the ligated DNA sample is converted into condensates by the addition of spermidine. The condensates were irradiated with UV light (t...

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“…The irradiation of AQs intercalated in duplex DNA gives efficient, piperidinerequiring strand cleavage selectively at GG sites by an electron transfer mechanism (16,17). The base sequence in PNA-1͞ DNA-1X was specifically designed to probe for the corresponding reaction in PNA͞DNA hybrids and to examine its mechanism.…”

Section: Resultsmentioning

confidence: 99%

“…Recent findings reveal that the light-induced reactions of a photosensitizer bound to duplex DNA by intercalation frequently generate alkalidependent cleavage sites selectively at the 5Ј-G of G-purine doublets, with a strong preference for GG steps. These photosensitizers include substituted anthraquinones (16,17), naphthalimides (18,19), a rhodium metal complex (14), and riboflavin (20). Breslin and Schuster (17) demonstrated unambiguously that GG-selective, photoinduced damage of DNA arises by an electron transfer pathway from an intercalated anthraquinone.…”

mentioning

confidence: 99%

Peptide nucleic acid–DNA duplexes: Long range hole migration from an internally linked anthraquinone

Armitage

Ly²,

Koch³

et al. 1997

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

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The discovery that peptide nucleic acids (PNA) mimic DNA and RNA by forming complementary duplex structures following Watson-Crick base pairing rules opens fields in biochemistry, diagnostics, and medicine for exploration. Progress requires the development of modified PNA duplexes having unique and well defined properties. We find that anthraquinone groups bound to internal positions of a PNA oligomer intercalate in the PNA-DNA hybrid. Their irradiation with near-UV light leads to electron transfer and oxidative damage at remote GG doublets on the complementary DNA strand. This behavior mimics that observed in related DNA duplexes and provides the first evidence for long range electron (hole) transport in PNA-DNA hybrid. Analysis of the mechanism for electron transport supports hole hopping.Peptide nucleic acid (PNA) oligomers are DNA͞RNA analogs (see Fig. 1) in which the natural sugar-phosphate backbone is replaced by a synthetic peptide backbone (1). PNA oligomers that contain purine and pyrimidine nucleobases hybridize with complementary DNA and RNA strands to form right-handed, double-helical complexes according to the Watson-Crick rules of hydrogen bond-mediated base pair formation (2). Although much has been learned about the structural (3) and thermodynamic (4) factors involved in hybridization, little is known about the chemical reactivity of PNA͞DNA hybrids. It is crucial to understand how PNA͞DNA hybrids mimic the reactions and functions of duplex DNA. Of immediate importance for their application as clinical diagnostic agents is investigation of the conductivity of DNA and its PNA analogs (5, 6).DNA must balance the dual requirements of chemical stability and ease of transcription and replication (7). It is clear that DNA is far from inert toward a variety of different reactive species, particularly oxidizing agents. Oxidative damage to DNA produced by normal metabolism, deep-UV laser irradiation (8), gamma rays (9), or pulse radiolysis (10) accumulates at guanine residues, an effect attributed to one-dimensional migration of a radical cation (''hole'') along the DNA helix (11). Both the low oxidation potential and reactivity of the guanine radical cation contribute to the effectiveness of guanine as a trap for the migrating hole. Because guanine lesions may be the major cause of mutations (12), intense attention is focused on understanding the conductivity properties of DNA to elucidate the mechanisms by which migration of oxidative damage occurs (13). In this regard, the recent reports by Barton and coworkers are particularly important (14, 15). They describe a system consisting of a rhodium complex that is covalently linked to one end of a DNA duplex. Irradiation caused damage to the DNA more than 30 Å from where the complex was presumed to intercalate. This observation opens up exciting opportunities to study the factors that control hole migration in nucleic acids.Photosensitizers often react with nucleic acids by single electron transfer to oxidize a base. Recent findings reveal that the...

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Cleavage of DNA by Irradiation of Substituted Anthraquinones: Intercalation Promotes Electron Transfer and Efficient Reaction at GG Steps

Cited by 173 publications

References 23 publications

Oxidation of Guanine in G, GG, and GGG Sequence Contexts by Aromatic Pyrenyl Radical Cations and Carbonate Radical Anions: Relationship between Kinetics and Distribution of Alkali-Labile Lesions

Oxidation of Guanine in G, GG, and GGG Sequence Contexts by Aromatic Pyrenyl Radical Cations and Carbonate Radical Anions: Relationship between Kinetics and Distribution of Alkali-Labile Lesions

Effect of condensate formation on long-distance radical cation migration in DNA

Peptide nucleic acid–DNA duplexes: Long range hole migration from an internally linked anthraquinone

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