Formation of Cyclobutane Thymine Dimers from UVA Photosensitization of Pyridopsoralen Monoadducted DNA

Guillo, Lidia Andreu; Beylot, Benedicte; Vigny, Paul; Spassky, Annick

doi:10.1111/j.1751-1097.1996.tb02470.x

Cited by 18 publications

(8 citation statements)

References 31 publications

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“…The low-lying pyrimidine triplet excited states were probed through induction of cyclobutane pyrimidine dimers as determined by digestion with T4 endonuclease V and sequencing gel electrophoresis of the bottom 59-labeled pyrimidine-rich strand. Consistent with previous observations (Guillo et al, 1996), the distribution of pyrimidine , average values; ss, single-stranded. The values for G 1 and G 2 for duplexes-IV to -VI are equals to those for duplex-III.…”

Section: Influence Of Basepair Stacking On the Variation In Quantum Esupporting

confidence: 92%

“…This observation raised the question of whether triplet-excited pyrimidine can be a substrate for ionization. To this end, we subjected a 98-bp EcoRI-HindIII excision fragment (Beylot and Spassky, 2001;Guillo et al, 1996) containing sequence-I to either a single high-intensity (E ¼ 0.1 J/cm 2 ) pulse or to multiple low-intensity pulses (E ¼ 0.002 J/cm 2 ) with the same total irradiation dose (Fig. 7).…”

Section: Influence Of Basepair Stacking On the Variation In Quantum Ementioning

confidence: 99%

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Origin of the Heterogeneous Distribution of the Yield of Guanyl Radical in UV Laser Photolyzed DNA

Angelov¹,

Beylot

Spassky

2005

Biophysical Journal

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Oxidative guanine lesions were analyzed, at the nucleotide level, within DNA exposed to nanosecond ultraviolet (266 nm) laser pulses of variable intensity (0.002-0.1 J/cm 2). Experiments were carried out, at room temperature, in TE buffer (20 mM Tris-HCl, pH 7.5; 1 mM EDTA) containing 35 mM NaCl, on 59-end radioactively labeled double-stranded and singlestranded oligomer DNA at a size of 33-37 nucleobases. Lesions were analyzed on polyacrylamide gel electrophoresis by taking advantage of the specific removal of 8-oxodG from DNA by the formamidopyrimidine DNA glycosylase (Fpg protein) and of the differential sensitivity of 8-oxodG and oxazolone to piperidine. The quantum yields of lesions at individual sites, determined from the normalized intensities of bands, were plotted against the irradiation energy levels. Simplified model fitting of the experimental data enabled to evaluate the spectroscopic parameters characterizing excitation and photoionization processes. Results show that the distribution of guanine residues, excited to the lowest triplet state or photoionized, is heterogeneous and depends on the primary and secondary DNA structure. These findings are generalized in terms of excitation energy and charge-migration mediated biphotonic ionization. On the basis of the changes in the yield of the guanyl radical resulting from local helical perturbations in the DNA p-stack, it can be assessed that the distance range of migration is ,6-8 bp.

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Section: Influence Of Basepair Stacking On the Variation In Quantum Esupporting

confidence: 92%

Section: Influence Of Basepair Stacking On the Variation In Quantum Ementioning

confidence: 99%

Origin of the Heterogeneous Distribution of the Yield of Guanyl Radical in UV Laser Photolyzed DNA

Angelov¹,

Beylot

Spassky

2005

Biophysical Journal

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“…It is interesting to note that the tetracyclic pyrido-coumarin 153 also acts as a thymine dimer photosensitiser [170].…”

Section: Anti-hiv Agentsmentioning

confidence: 99%

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Kulkarni¹,

Kulkarni²,

Chao³

et al. 2006

CMC

225

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Coumarins, also referred as benzopyran-2-ones, and their corresponding nitrogen counterpart, 1-azacoumarins also referred to as carbostyrils, are a family of nature-occurring lactones and lactams respectively. The plant extracts containing coumarin-related heterocycles, which were employed as herbal remedies in early days, have now been extensively studied for their biological activities. These investigations have revealed their potentials as versatile biodynamic agents. For example, coumarins with phenolic hydroxyl groups have the ability to scavenge reactive oxygen species and thus prevent the formation of 5-HETE and HHT in the arachidonic pathway of inflammation suppression. Recent in vivo studies have revealed the role of coumarins in hepatotoxicity and also in depletion of cytochrome P450. Similarly 1-azacoumarins which is part of quinoline alkaloids, are known for their diverse biological activity and recently, a 6-functionalized 1-aza coumarins are undergoing human clinical trials as an orally active anti-tumor drug in view of its farnesyl protein-inhibiting activity in the nanomolar range. Furthermore, several synthetic coumarins with a variety of pharmacophoric groups at C-3, C-4 and C-7 positions have been intensively screened for anti-microbial, anti-HIV, anti-cancer, lipid-lowering, anti-oxidant, and anti-coagulation activities. Specifically, coumarin-3-sulfonamides and carboxamides were reported to exhibit selective cytotoxicity against mammalian cancer cell lines. The C4-substituted aryloxymethyl, arylaminomethyl, and dichloroacetamidomethyl coumarins, along with the corresponding 1-azacoumarins, have been demonstrated to be potential anti-microbial and anti-inflammatory agents. To expand the structural diversity of synthetic courmarins for biological functions, attempts have also been made to attach a chloramphenicol side chain at C-3 position of courmarin. In addition, the bi- and tri-heterocyclic coumarins and 1-azacoumarins with benzofuran, furan and thiazole ring systems along with biocompatible fragments like vanillin have shown remarkable potency as anti-inflammatory agents in animal models. Photobiological studies on pyridine-fused polycyclic coumarins have highlighted their potential as thymine dimer photosensitisers and the structurally related compounds of both coumarin and carbostyrils have also been found to act via the DNA gyrase pathway in their anti-bacterial activity. Apart from the above works, the present review also addresses the potential roles of coumarins and carbostyrils as protease inhibitors, or fluorescent probes in mechanistic investigation of biochemical pathways, and their application for QSAR in theoretical studies. Though 1-Azacoumarins have received less attention as compared to coumarins in the literature, an attempt has been made to compare both the systems at various stages, so that it can spark new thoughts on synthetic methodologies, reactivity pattern and biological activities.

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“…Sequence recognition would arise from the inherent sequence-dependent ability to adopt the conformation required for protein binding in the transient, biologically active complex. In an attempt to reveal intrinsic helical properties of the I-SceI nucleic acid target, we used this sequence as substrate in earlier studies analyzing the mechanisms of DNA chemical reactions and photosensitization processes (9,10,11,12). We found evidence that the conformation of the helix deviates from the ideal B-form duplex along two segments of three and five base pairs located at a distance of approximately one helical turn, respectively, upstream and downtream from the site of junction of the two exons (9).…”

mentioning

confidence: 99%

Chemical Probing Shows That the Intron-encoded Endonuclease I-SceI Distorts DNA through Binding in Monomeric Form to Its Homing Site

Beylot¹,

Spassky

2001

Journal of Biological Chemistry

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Despite its small size (27.6 kDa), the group I intronencoded I-SceI endonuclease initiates intron homing by recognizing and specifically cleaving a large intronless DNA sequence. Here, we used gel shift assays and footprinting experiments to analyze the interaction between I-SceI and its target. I-SceI was found to bind to its substrate in monomeric form. Footprinting using DNase I, hydroxyl radical, phenanthroline copper complexes, UV/DH-MePyPs photosensitizer, and base-modifying reagents revealed the asymmetric nature of the interaction and provided a first glimpse into the architecture of the complex. The protein interacts in the minor and major grooves and distorts DNA at three distinct sites: one at the intron insertion site and the other two, respectively, downstream (؊8, ؊9) and upstream (؉9, ؉10) from this site. The protein appears to stabilize the DNA curved around it by bridging the minor groove on one face of the helix. The scissile phosphates would lie on the outside of the bend, facing in the same direction relative to the DNA helical axis, as expected for an endonuclease that generates 3 overhangs. An internally consistent model is proposed in which the protein would take advantage of the concerted flexibility of the DNA sequence to induce a synergistic binding/kinking process, resulting in the correct positioning of the enzyme active site.I-SceI is a homing endonuclease encoded by the mobile group I intron of the large rRNA gene of Saccharomyces cerevisiae (1, 2). This family of enzymes mediates the propagation of the intron by cutting intronless genes at the site of intron insertion (reviewed in Ref.3). Like restriction enzymes, homing endonucleases cleave double-stranded DNA with high specificity in the presence of divalent metal ions. However, they differ from restriction endonucleases in their recognition properties and structures, as well as in their genomic location (4). In particular, whereas restriction enzymes have short recognition sequences (3-8 bp), 1 homing endonucleases, despite their small size, recognize long DNA sequences (12-40 bp). They have been classified into four families on the basis of both their sequence motifs and DNA cleavage mechanism (3). to cleave DNA within its recognition sequence and leaves a 4-bp overhang presenting a 3Ј-hydroxyl terminus (5, 6). The enzyme displays a low turnover, probably because of its strong affinity for one of the products of the cleavage reaction (7).The interaction of homing endonucleases with their substrates raises an interesting question common to all the gene-regulatory proteins, namely: how can a small protein specifically recognize and modify a long DNA sequence? Understanding the molecular basis of such a mechanism is essential for elucidating many aspects of cellular control and is a prerequisite in any rational drug design program. It is clearly established that local and global DNA structural features that are highly sequence-dependent, play a primary role in the dynamics of protein-DNA recognition (8). Sequence recognition would...

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Formation of Cyclobutane Thymine Dimers from UVA Photosensitization of Pyridopsoralen Monoadducted DNA

Cited by 18 publications

References 31 publications

Origin of the Heterogeneous Distribution of the Yield of Guanyl Radical in UV Laser Photolyzed DNA

Origin of the Heterogeneous Distribution of the Yield of Guanyl Radical in UV Laser Photolyzed DNA

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Chemical Probing Shows That the Intron-encoded Endonuclease I-SceI Distorts DNA through Binding in Monomeric Form to Its Homing Site

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