A-DNA and B-DNA: Comparing Their Historical X-ray Fiber Diffraction Images

Lucas, A. A.

doi:10.1021/ed085p737

Cited by 8 publications

(4 citation statements)

References 11 publications

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“…3c ). The fiber diffraction pattern from YTMA-DNA is unmistakably representative of B-form DNA, which can be identified by a repeating diamond pattern and layer lines that form a distinct central cross (lines 1–3 and 5) and intense meridian arcs (line 10) 28 – 30 . Thus, the circular dichroism spectrum and the fiber diffraction pattern of YTMA-DNA are both consistent with a B-DNA structure.…”

Section: Resultsmentioning

confidence: 99%

Toxicity and repair of DNA adducts produced by the natural product yatakemycin

2017

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Yatakemycin (YTM) is an extraordinarily toxic DNA alkylating agent with potent antimicrobial and antitumor properties and the most recent addition to the CC-1065 and duocarmycin family of natural products. While bulky DNA lesions the size of those produced by YTM are normally removed from the genome by the nucleotide excision repair (NER) pathway, YTM adducts are also a substrate for the bacterial DNA glycosylases AlkD and YtkR2, unexpectedly implicating base excision repair (BER) in their elimination. The reason for the extreme toxicity of these lesions and the molecular basis for how they are eliminated by BER have been unclear. Here, we describe the structural and biochemical properties of YTM adducts responsible for their toxicity, and define the mechanism by which they are excised by AlkD. These findings delineate an alternative strategy for repair of bulky DNA damage and establish the cellular utility of this pathway relative to that of NER.

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Section: Resultsmentioning

confidence: 99%

Toxicity and repair of DNA adducts produced by the natural product yatakemycin

2017

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“…Typical transmission diffraction patterns of crystalline DNA fibers include several unique features that allow studying the orientation and structure of various molecular subgroups (detailed description of these features and their structural origins are discussed in other sources, e.g., ref. ). The main feature is the strongest reflection on the meridian that corresponds to the inter‐base distance in the double helix.…”

Section: Resultsmentioning

confidence: 97%

“…The main feature is the strongest reflection on the meridian that corresponds to the inter‐base distance in the double helix. Another key feature of DNA fiber diffraction is the x‐shaped layer lines that originate from the ordered helical arrangement of the DNA backbone . We performed transmission XRD on an approximately 400 µm thick DNA nanofiber bundle (measured from SEM images).…”

Section: Resultsmentioning

confidence: 99%

Continuous DNA Nanofibers with Extraordinary Mechanical Properties and High Molecular Orientation

Maleckis¹,

Dzenis

2018

Macro Materials & Eng

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The dual nano–macro nature of continuous nanofibers holds great promise in bridging the unique nanoscale properties of DNA to macroscopic devices. However, due to the limitations of existing manufacturing methods, controlled fabrication of macroscopically long DNA nanofibers has not been achieved so far. This article presents optimized electrospinning of substrate‐free and uniform DNA nanofibers with macroscopic lengths and diameters ranging from ultrafine (<50 nm) to submicron scale. Mechanical tests of individual DNA nanofibers show highly nonlinear deformation in tension that is accompanied by unexpectedly high true strength (>1 GPa) and toughness (>200 MPa) values for the thinnest tested nanofibers. Molecular characterization with X‐ray diffraction and polarized Raman spectroscopy indicates that the high mechanical properties and their unusual size effects in DNA nanofibers originate from the high molecular alignment that is preserved with the increase in diameter. These results show that electrospun DNA nanofibers can overcome the weaknesses of DNA nanostructures manufactured by other top‐down and bottom‐up methods and that they offer novel capabilities for the DNA‐based nanomaterials.

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“…to obtain all known DNA forms and their transitions in fiber diffraction experiments (Millane et al, 1984;Lucas, 2008). Transition between B-DNA and A-DNA can be induced by the change of relative humidity at a specific salt concentration (Arnott, 2006), as water molecules stabilize B-DNA over A-DNA through the water coordination in the minor groove (Calladine and Drew, 1984).…”

Section: Dna Hydrationmentioning

confidence: 99%

Structural studies of AT-rich DNA

Acosta Reyes

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Non-coding DNA is rich in adenines and thymines. Their unique properties, such as high polymorphism, flexibility, transitional states that lead to DNA hairpin formation and the possibility to adopt either Watson-Crick or Hoogsteen base pairing conformations, in conjunction with its distribution in genomes, suggest the possibility of a structural role. In spite of that, the available structural information for AT-rich oligonucleotides in databases such as Protein Data Bank (PDB) and Nucleic Acids Data Bank (NDB) is very limited in comparison to oligonucleotides of high CG content. These facts have motivated us to undertake the study of the structural characteristics specific for AT-rich oligonucleotides. X-ray crystallography was used for the study of AT-rich oligonucleotides with particular sequences, such as a palindromic sequence suitable for the formation of a DNA hairpin, alternating-AT and A-tracts. Additionally, dynamic light scattering was used to identify the most suitable conditions for initial crystallization trials. The unique properties of AT-rich sequences such a high polymorphism and flexibility constitute ideal features for their possible structural role, but also present difficulties for crystal organization, as required for X-ray crystallography. In several cases, only poor diffracting crystals were obtained. The following structural features were identified in the AT-rich oligonucleotides studied by us: Crystals of the oligonucleotide d((AT)3T3A(AT)3) in a DNA hairpin conformation have been obtained. The structure of the loop appears to be highly variable; as a result, the crystals have low resolution. A tentative model of the hairpin structure has been proposed. The d(A4T4) octamer was crystallized as a complex with the CD27 drug. This drug has previously demonstrated a high antiprotozoal activity, in particular against Plasmodium falciparum and Trypanosoma brucei. The structure obtained shows how the CD27 drug fills completely the minor groove and interacts with molecules of stacked oligonucleotides and with the backbone of neighboring duplexes, stabilizing a complex organization. The elevated number of occurrences of the motif A4 in the genomes of Plasmodium falciparum and particularly in the kDNA of Trypanosoma brucei represents a suitable target for the CD27 drug. The d(CG(AT)4CG)2 dodecamer in presence of Ni2+ crystallizes in the typical pseudo four-way helix-helix junction configuration, with extra-helical and terminal guanines coordinated to nickel. A bis-coordination of Ni2+ with two stacked helical guanines was identified in the structure of d(CG(AT)4CG)2 in the presence of Ni2+ and the CD27 drug. The oligonucleotide d(A6T6)2 in the presence of Mn2+ and the S1010 drug in the crystallization conditions acquires a coiled-coil conformation. The following structures were determined as part of a collaboration in several other projects: The structure of the oligonucleotide d(AATAAATTTATT)2 in presence of different ions exhibits the typical high polymorphism of AT-rich DNA. The ions present in the crystallization conditions modulate the organization of duplexes, most likely through changes in the ionic atmosphere around the DNA duplexes. The structure of the oligonucleotide d(ATTAAT)2 in Hoogsteen conformation demonstrates that any all-AT sequence may adopt the Hoogsteen conformation under appropriate conditions. The structures of d(CGAATTAATTCG)2, d(ATATCGATAT)2 and d(ATATGCATAT)2 in the presence of ligands (ions, peptide or protein), were successfully determined. In the case of d(ATATGCATAT)2 a coiled-coil conformation was found in the presence of Mg2+. El DNA no codificant es ric en adenines i timines (AT). Les seves propietats úniques com alt polimorfisme, flexibilitat, estats de transició que porten a la formació d'estructures bucle i la possibilitat d'adoptar conformacions de parells de bases Watson-Crick o Hoogsteen, conjuntament amb la seva distribució en genomes, suggereixen la possibilitat d'un rol estructural. Malgrat això, la informació disponible per oligonucleòtids rics en AT en bases de dades (PDB i NDB) és molt limitada en comparació amb la dels oligonucleòtids d'alt contingut en citosina i guanina. Aquests fets ens han motivat per emprendre l'estudi de les característiques estructurals d'oligonucleòtids rics en AT. La cristal.lografia de raigs X s'ha fet servir per l'estudi d'oligonucleòtids rics en AT de seqüències concretes, com ara la seqüència palindròmica per a la formació d'estructures bucle del DNA, l'alternant AT i la d'adenines consecutives. A més, es va utilitzar la tècnica de dispersió dinàmica de llum per identificar les condicions òptimes per a les proves inicials de cristal.lització. Les propietats úniques de les seqüències riques en AT com l'alt polimorfisme i la flexibilitat constitueixen propietats ideals pel possible rol estructural, però d'altra banda comporten dificultats per a l'organització molecular requerida per la cristal·lografia de raigs X. En diversos casos, només es van obtenir cristalls amb difraccions desordenades i de baixa resolució. Dels oligonucleòtids rics en AT estudiats, es van identificar les següents característiques estructurals: Amb l'oligonucleòtid d((AT)3T3A(AT)3) es van obtenir cristalls amb la conformació bucle. L'estructura del bucle es mostra altament variable; com a resultat, els cristalls presenten baixa resolució. Es proposa un model temptatiu del bucle. Es va cristal.litzar el complex de l'octàmer d(A4T4) amb el fàrmac CD27. Aquest fàrmac ha demostrat prèviament una alta activitat antiprotozoària, en particular pel Plasmodium falciparum i pel Trypanosoma brucei. L'estructura resolta mostra com el CD27 omple el solc estret completament i interactua amb molècules d'oligonucleòtics apilats i amb la cadena de fosfats dels dúplexs veïns, estabilitzant una organització complexa. L'elevat nombre d'incidències del motiu A4 en els genomes del Plasmodium falciparum i particularment en el k-DNA del Trypanosoma brucei, representa un lloc d'unió adient per el CD27. El dodecàmer d(CG(AT)4CG)2 en presència de Ni2+ cristal·litza en la típica configuració en pseudo-intersecció hèlix-hèlix de quatre vies amb les guanines extra-helicoïdals i terminals coordinades amb níquel. Es va identificar una doble coordinació de Ni2+ amb dos guanines apilades en l'estructura de d(CG(AT)4CG)2 en presència del fàrmac CD27. L'oligonucleòtid d(A6T6)2 en presència de Mn2+ i del fàrmac S1010 adopta una conformació en superhèlix (coiled-coil). Les següents estructures es van resoldre en col·laboració amb altres projectes: Les estructures de l'oligonucleòtid d(AATAAATTTATT)2 obtingudes en presència de diferents ions mostra el típic polimorfisme del DNA ric en AT. Els ions presents modulen l'organització de dúplexs, probablement degut a canvis en la atmosfera iònica al voltant del DNA. L'estructura de l'oligonucleòtid d(ATTAAT)2 en conformació Hoogsteen indica que qualsevol seqüència completament AT podria adoptar la conformació Hoogsteen en condicions adients. L'estructura dels oligonucleòtids d(CGAATTAATTCG)2, d(ATATCGATAT)2 i d(ATATGCATAT)2 en presència de lligands (ions, pèptid i proteïna), van ser resoltes amb èxit. En el cas de d(ATATGCATAT)2, es va trobar una conformació en superhèlix en presència de Mg2+.

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A-DNA and B-DNA: Comparing Their Historical X-ray Fiber Diffraction Images

Cited by 8 publications

References 11 publications

Toxicity and repair of DNA adducts produced by the natural product yatakemycin

Toxicity and repair of DNA adducts produced by the natural product yatakemycin

Continuous DNA Nanofibers with Extraordinary Mechanical Properties and High Molecular Orientation

Structural studies of AT-rich DNA

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