Дисертації: "DNA"

1

Lo, Allen Tak Yiu. "Protein dynamics on the lagging strand during DNA synthesis." Thesis, School of Chemistry, 2012. https://ro.uow.edu.au/theses/3684.

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DNA replication is one of the vital processes in the cell; it duplicates chromosomal DNA before a cell divides. In all organisms, DNA synthesis on the leading-strand template occurs continuously, whereas on the lagging strand a different mechanism is required. Due to the anti-parallel structure of double-stranded DNA, lagging-strand synthesis requires repeated RNA priming by a specialist primase and synthesis of short Okazaki fragments. How proteins carry out this dynamic process is still unknown. For Escherichia coli DNA replication, a lagging-strand three-point switch was proposed in 1999 to explain priming by DnaG primase while it is associated with the DnaB6 helicase, and its subsequent hand-off from the primer to the χ subunit of DNA polymerase III holenzyme to enable primer utilization for Okazaki fragment synthesis. The main aims of this project were to study the interactions involved in this switch to understand better how the proteins coordinate their roles during lagging-strand DNA synthesis.

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2

Martin, Eleyna. "Initiation of DNA replication in Bacillus subtilis : structural studies of the DnaA-DnaD interaction." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/53443/.

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Replication of genetic information is a vital process across all domains of life. Bacillus subtilis is considered the gram-positive model bacterium for studying DNA replication (Escherichia coli has been studied extensively as the gram-negative model) and is most representative of the ancestral phylum of prokaryotes. DNA replication has three distinct stages; initiation, elongation and termination. Replication initiation is the focus of this research and this process occurs at a single origin conserved throughout bacteria, termed oriC. B. subtilis primosomal machinery is formed of replication initiator proteins DnaA, DnaD and DnaB, the helicase loader DnaI, replicative helicase DnaC and primase DnaG. The role of the initiator proteins is to melt the DNA double helix and enable loading of the hexameric ring helicase onto each strand of DNA for bidirectional replication. Initiation is the first stage in DNA replication and despite its importance the molecular mechanisms of replication initiation remain largely unclear. The work presented in this thesis has focussed on the essential interaction between replication initiator proteins DnaA and DnaD, with an aim to characterise their binding interface and reveal molecular details of their mechanisms of interaction during DNA replication initiation. The direct interaction between isolated DnaA domain I and DnaD DDBH2 domain was detected by NMR spectroscopy which was subsequently used to identify the specific residues involved and characterise the nature of the binding interface. The kinetics of the interaction were investigated by SPR and computational techniques were used to model the DnaA-DnaD complex. This structural characterisation of the DnaA-DnaD interaction provides greater understanding of the molecular mechanisms of DnaA and DnaD during DNA replication initiation.

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3

Komori, Hirofumi. "Structural studies on DNA-binding proteins : DNA replication initiator and DNA photolyase." 京都大学 (Kyoto University), 2002. http://hdl.handle.net/2433/150005.

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4

Bandholtz, Lisa Charlotta. "DNA vaccines and bacterial DNA in immunity /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-340-6/.

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5

Richardson, James Alistair. "Novel DNA probes for sensitive DNA detection." Thesis, University of Southampton, 2010. https://eprints.soton.ac.uk/173981/.

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The ability to detect and interrogate DNA sequences allows further understanding and diagnosis of genetic disease. The ability to perform such analysis of genetic material requires highly selective and reliable technologies. Furthermore techniques which can use simple and cheap equipment allow the use of such technologies for point of care analysis. Described in this thesis are two novel DNA probe systems designed for mutation discrimination and sequence recognition of PCR products. A homogenous PCR system using HyBeacons® which utilise FRET to produce a three probe multiplex system and surface enhanced Raman detection method. Both of these systems allow multiplex detection of PCR products and mutation discrimination by melting temperature analysis. The research reported includes investigations into the effects of different modifications to improve the performance of HyBeacon® probes as well as the effect of different dyes in a FRET system, including unique changes in the optical properties of such dyes. Also a novel method of performing melting temperature analysis using an electrochemical potential is reported. In addition to the detection methods described this thesis includes initial work into the stabilisation of quantum dot nanoparticles for their use in aqueous systems as a potential alternative to fluorescent organic molecules.

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6

Boal, Amie Kathleen Parker Carl Stevens Barton Jacqueline K. "DNA-mediated charge transport in DNA repair /." Diss., Pasadena, Calif. : California Institute of Technology, 2008. http://resolver.caltech.edu/CaltechETD:etd-06022008-092549.

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7

Lo, Pik Kwan Peggy. "Supramolecular DNA chemistry: assembly of DNA nanotubes and templated synthesis of DNA-mimetic polymers." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95152.

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DNA has emerged as a promising template for the programmable assembly of structures on the nanometer scale. In particular, DNA nanotubes hold promise for a number of biological and materials applications, because of their high aspect ratio and encapsulation potential. Current construction methods result in symmetrical and cylindrical assemblies that are totally double-stranded, and are long and polydisperse. In order to investigate DNA nanotubes for applications as well-defined molecular hosts and one-dimensional templates, better control over their geometry, stiffness and porosity, ability to encapsulate and length needs to be achieved. Specifically, the first section of this thesis will describe (a) a modular approach to construct DNA nanotubes of geometrically well-defined triangular and square-shapes, which can exist in either double- and single-stranded forms with different stiffnesses, (b) the construction of DNA nanotubes with longitudinal variation by alternating larger and smaller capsules along the tube length, the encapsulation of guest molecules within these DNA nanotubes as well as their selective release with externally added DNA strands, (c) the use of a DNA-templated approach to produce nanotubes with controlled pre-determined lengths of 1 μm, and 500 nm and narrow length distributions, and the encapsulation of gold nanoparticles within these well-defined nanotubes to form finite lines of gold nanoparticles with longitudinal plasmon coupling. While DNA is a very promising construction material, it suffers from serious drawbacks for practical applications in materials science and biology. DNA is difficult and expensive to obtain in large quantities, and has limited long-term stability. On the other hand, synthetic polymers are routinely used as building blocks for nanostructured materials, with multiple applications in areas ranging from optics and data storage, to separation science and biology. Thus, an important challenge is the creation of
L'ADN s'est récemment manifesté comme un matériau prometteur pour l'assemblage programmable de structures à l'échelle nanométrique. En particulier, les nanotubes d'ADN sont intéressants pour leurs applications en science des matériaux et en biologie, en raison de leur aspect linéaire et leur potentiel d'encapsulation. Les méthodes courantes de leur synthèse produisent des assemblées symétriques et cylindriques totalement constituées de doubles brins d'ADN longs et polydisperses. Afin d'examiner les nanotubes d'ADN pour leurs applications comme des hôtes moléculaires à structure bien-définie et comme modèles unidimensionnels, des méthodes de synthèse qui mènent à un plus haut niveau de contrôle de leur géométrie, rigidité, porosité, capacité d'encapsulation et longueur doivent être développées. Plus précisément, la première section de cette thèse décrira (a) une approche modulaire pour construire des nanotubes d'ADN géométriquement bien définis, triangulaires ou carrés, et pouvant exister en formes d'ADN double-brin ou brin simple avec des différences de rigidité, (b) la construction des nanotubes d'ADN avec une variation longitudinale, en alternant les grandes et les petites capsules le long du tube, et l'encapsulation de matériaux invités au sein de ces nanotubes d'ADN, ainsi que leur libération sélective sous l'action de brins d'ADN externes ajoutés, (c) l'utilisation de l'approche d'un modèle d'ADN pour produire des nanotubes avec des longueurs contrôlées et prédéterminées de 1 µm ou de 500 nm et des distributions de longueurs étroites, et l'encapsulation de nanoparticules d'or au sein de ces nanotubes bien définis pour former des lignes de longueurs bien définies de nanoparticules d'or avec un couplage plasmonique longitudinal. Bien que l'ADN soit une molécule très intéressante pour l'auto-assemblage de structures, son utilisation comme un outil dans les applications pratiques en science des maté

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8

Araki, Kasumi. "Dual roles for DNA polymerase η in homologous DNA recombination and translesion DNA synthesis". Kyoto University, 2006. http://hdl.handle.net/2433/143860.

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9

CRISTOFALO, MATTEO. "Nanomechanics of DNA and DNA-ligand interactions: focus on structural polymorphism and DNA condensation." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2019. http://hdl.handle.net/10281/241313.

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In the last few decades, the constant development of novel microscopy techniques have created the basis for a new paradigm in the field of biophysics. Single-molecule techniques enabled to carry out experiments providing new information: the nanomanipulation of individual biomolecules revealed unknown insights into the elasticity and mechanics of molecules, improving the understanding of the fundamental relation between structural properties and biological functions. In particular, an AFM and mostly a MT setup were used during this thesis work, both located in biophysics laboratory of Prof. Francesco Mantegazza, at the University of Milano-Bicocca. Similar issues were encountered at the cellular level, because bulk experiments of conventional microscopy techniques provide information on average only, without taking into account the intrinsic biological heterogeneity. Recent developments in microfluidics enabled to follow individual cells over a long time and under controlled conditions. During the last part of this thesis project I used one of these microfluidic devices to perform time-lapse microscopy experiments at the single-cell level. These experiments were carried out during a visiting period of seven months in Prof. Pietro Cicuta’s laboratory, in Cavendish laboratory at University of Cambridge. In this thesis I dealt with three main research topics: • DNA structural polymorphism • nanomechanics of DNA-ligand interactions • the dual role of H-NS protein: DNA condensation and gene regulation The study of the conformational changes of DNA, namely the property of structural polymorphism, is addressed during two projects: one about the nanomechanics of a DNA analogue and another concerning the behavior of DNA at high supercoiling. The study of a DNA analogue enables to observe how a chemical modification of nucleotides can induce structural re- arrangements of the double-helix, biasing towards an A-like-form of DNA. The regimes of high supercoiling, both positive and negative supercoiling, show instead how an applied torsion at a certain forces can promote the formation of plectonemes or denaturation bubbles, which are conditions that favor particular structural transitions. The second major theme concerns the analysis of the nanomechanics of DNA-ligand complexes, particularly the interactions of DNA with anticancer drugs or with the H-NS protein and the crowding agent PEG. The project about the interactions between DNA and drugs clearly shows how the mechanical properties and the stability of DNA change due to the binding with compounds commonly used in clinics to treat tumors. On the other hand, the H-NS protein forms relatively stable DNA loops and influences the stability of the double helix, as well as the crowding agent. The protein binding mechanism has a preference for some DNA sequences and an unexpected concentration-dependent behavior. The analysis of the the DNA-H-NS interactions also enables, particularly in crowding conditions, to better understand the mechanism of DNA condensation inside the cell, one of the biological roles of H-NS. The second important function of this NAP is the gene regulation. To investigate the dual role of H-NS in great detail two complementary techniques have been combined. The nanoma- nipulation technique is employed to observe the structural role of H-NS and its combined activity with a crowding agent leading to a clear and abrupt compaction of DNA. Time-lapse fluorescence microscopy is instead used to study the regulatory role of the protein, more precisely the gene silencing mechanism, at the single-cell level. This activity has also a strong influence in the cell physiology, by significantly changing the growth rate of bacteria.
In the last few decades, the constant development of novel microscopy techniques have created the basis for a new paradigm in the field of biophysics. Single-molecule techniques enabled to carry out experiments providing new information: the nanomanipulation of individual biomolecules revealed unknown insights into the elasticity and mechanics of molecules, improving the understanding of the fundamental relation between structural properties and biological functions. In particular, an AFM and mostly a MT setup were used during this thesis work, both located in biophysics laboratory of Prof. Francesco Mantegazza, at the University of Milano-Bicocca. Similar issues were encountered at the cellular level, because bulk experiments of conventional microscopy techniques provide information on average only, without taking into account the intrinsic biological heterogeneity. Recent developments in microfluidics enabled to follow individual cells over a long time and under controlled conditions. During the last part of this thesis project I used one of these microfluidic devices to perform time-lapse microscopy experiments at the single-cell level. These experiments were carried out during a visiting period of seven months in Prof. Pietro Cicuta’s laboratory, in Cavendish laboratory at University of Cambridge. In this thesis I dealt with three main research topics: • DNA structural polymorphism • nanomechanics of DNA-ligand interactions • the dual role of H-NS protein: DNA condensation and gene regulation The study of the conformational changes of DNA, namely the property of structural polymorphism, is addressed during two projects: one about the nanomechanics of a DNA analogue and another concerning the behavior of DNA at high supercoiling. The study of a DNA analogue enables to observe how a chemical modification of nucleotides can induce structural re- arrangements of the double-helix, biasing towards an A-like-form of DNA. The regimes of high supercoiling, both positive and negative supercoiling, show instead how an applied torsion at a certain forces can promote the formation of plectonemes or denaturation bubbles, which are conditions that favor particular structural transitions. The second major theme concerns the analysis of the nanomechanics of DNA-ligand complexes, particularly the interactions of DNA with anticancer drugs or with the H-NS protein and the crowding agent PEG. The project about the interactions between DNA and drugs clearly shows how the mechanical properties and the stability of DNA change due to the binding with compounds commonly used in clinics to treat tumors. On the other hand, the H-NS protein forms relatively stable DNA loops and influences the stability of the double helix, as well as the crowding agent. The protein binding mechanism has a preference for some DNA sequences and an unexpected concentration-dependent behavior. The analysis of the the DNA-H-NS interactions also enables, particularly in crowding conditions, to better understand the mechanism of DNA condensation inside the cell, one of the biological roles of H-NS. The second important function of this NAP is the gene regulation. To investigate the dual role of H-NS in great detail two complementary techniques have been combined. The nanoma- nipulation technique is employed to observe the structural role of H-NS and its combined activity with a crowding agent leading to a clear and abrupt compaction of DNA. Time-lapse fluorescence microscopy is instead used to study the regulatory role of the protein, more precisely the gene silencing mechanism, at the single-cell level. This activity has also a strong influence in the cell physiology, by significantly changing the growth rate of bacteria.

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10

Grundström, Malin. "DNA : Att tillvarata DNA på ett rättssäkert sätt." Thesis, Umeå University, Basic training programme for Police Officers, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-27188.

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Syftet med arbetet är att belysa problematiken kring DNA som ett bevisinstrument, hur de olika analysformerna går till samt att påvisa vikten av att även polispersonal i yttre tjänst förstår hur och varför det är så viktigt att det tillvaratas på rätt sätt. Det finns mycket litteratur om DNA och jag har försökt begränsa mitt material till de delar som kan intressera poliser. Jag har även försökt att förklara DNA på ett så lätt sätt som möjligt för att den som inte är så bevandrad i biologi skall kunna förstå ett ändå mycket komplext ämne. Företrädelsevis har jag använt mig av skriftlig litteratur i form av handböcker för kriminaltekniker, föreläsningsanteckningar från Rättsmedicin för Jurister och sökningar på Internet ex. SKL’s hemsida. I arbetet har jag först gått igenom bakgrunden rent historiskt kring DNA, från första upptäckten av hur egenskaper ärvs 1865 till modern tid då DNA används som bevis i rättegångar. Resultatet har jag redovisat som ett fingerat ”case” där jag låtit huvudpersonerna agera utifrån vad man ska tänka på när man säkrar DNA-spår och låtit dem följa hela kedjan ända till analyssvar och sedermera en dom i tingsrätten. Eftersom DNA är ett mycket känsligt spår är det viktigt att det tillvaratas på rätt sätt för att det inte skall kontamineras (dvs. smittas av spårsäkrarens eget DNA) och även förstöras. Detta för att kunna säkra att rätt person döms för brottet.

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11

Pearson, Christopher Edmund. "DNA cruciforms and mammalian origins of DNA replication." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28503.

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The objective of the research in this thesis is to investigate, at the molecular level, the sequences and/or structures involved in the initiation of mammalian DNA replication and to investigate the protein interactions with DNA cruciforms which have been implicated in the process of replication initiation. Four plasmids containing monkey (CV-1) early replicating nascent origin enriched sequences (ors), which had been shown previously to replicate autonomously in transfected CV-1, COS-7 and HeLa cells, were used in the establishment of an in vitro DNA replication system that uses HeLa cell extracts. The in vitro replication system is dependent upon the presence of an ors sequence, and HeLa cell extracts. Mapping experiments indicate that there is preferential nucleotide incorporation in the ors sequences, suggesting site-specific initiation, and that replication is bidirectional and semiconservative. Electron microscopy confirmed that in vitro initiation occurs within the ors sequence.
Prokaryotic and eukaryotic viral replication origins, mammalian origin enriched sequences (ors) and other mammalian early replicating sequences contain AT-rich sequences and inverted repeats, which have the potential to form bent and cruciform (stem-loop) DNA structures, respectively. Cruciforms have been postulated to form transiently at or near origins to serve as recognition structures for initiator proteins. Using a stable-DNA cruciform as a binding substrate in a band-shift assay, a novel DNA binding activity with specificity for the cruciform-containing DNA and no apparent sequence-specificity was identified in HeLa cell extracts. The activity is protein-dependent and is void of detectable nuclease activity. Cruciform-specific binding was observed to be maximal in early-S phase extracts. A novel cruciform binding protein (CBP) with an apparent molecular weight of 66 kDa was enriched from HeLa cell extracts. Footprinting experiments localized the CBP-DNA cruciform interaction to the four-way junction at the base of the cruciform. CBP appears to interact with the elbow junctions in an asymmetric fashion. Upon CBP binding, structural distortions were observed at the cruciform stems and at a DNA region distal to the junction.

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12

Morant, Nick. "Novel thermostable DNA polymerases for isothermal DNA amplification." Thesis, University of Bath, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.667735.

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DNA polymerases play a fundamental role in the transmission and maintenance of genetic information and have become an important in vitro diagnostic and analytical tool. The Loop-mediated isothermal DNA amplification (LAMP) method has major applications for disease and pathogen detection and utilises the unique strand-displacement activity of a small group of thermostable DNA polymerases. The Large (Klenow-like) Fragment of Geobacillus stearothermophilus DNA polymerase I (B.st LF Pol I) currently serves as the enzyme of choice for the majority of these isothermal reactions, with few alternatives commercially available. An increasing need for point-of-care nucleic acid diagnostics is now shifting detection methods away from traditional laboratory based chemistries, such as the polymerase chain reaction (PCR), in favour of faster, and often simpler, isothermal methods. It was recognised that in order to facilitate these rapid isothermal reactions there was a requirement for alternative thermostable, strand-displacing DNA polymerases and this was the basis of this thesis. This thesis reports the successful identification of polymerases from Family A, chosen for their inherent strand-displacement activity, which is essential for the removal of RNA primers of Okazaki fragments during lagging-strand DNA synthesis in vivo. Twelve thermophilic organisms, with growth temperature ranges between 50oC and 80oC, were identified and the genomic DNA extracted. Where DNA sequences were unavailable, a gene-walking technique revealed the polA sequences, enabling the Large Fragment Pol I to be cloned and the recombinant protein over-expressed in Escherichia coli. A three-stage column chromatography purification permitted the characterisation of ten newly identified Pol I enzymes suitable for use in LAMP. Thermodesulfatator indicus (T.in) Pol I proved to be the most interesting enzyme isolated. Demonstrating strong strand-displacement activity and thermostability to 98oC, T.in Pol I is uniquely suitable to a newly termed heat-denaturing LAMP (HD-LAMP) reaction offering many potential advantages over the existing LAMP protocol. The current understanding of strand-displacement activity of Pol I is poorly understood. This thesis recognised the need to identify the exact regions and motifs responsible for this activity of the enzyme, enabling potential enhancements to be made. Enzyme engineering using site-directed mutagenesis and the formation of chimeras confirmed the importance of specific subdomains in strand-separation activity. With this knowledge, a unique Thermus aquaticus (T.aq) Pol I mutant demonstrated sufficient strand-displacement activity to permit its use in LAMP for the first time. The fusion of Cren7, a double-stranded DNA binding protein, to Pol I for use in LAMP is also reported. Although the fusion construct was found to reduce amplification speed, enhancements were observed in the presence of increased salt concentrations and it is suggested here as a means for future enzyme development.

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13

Carson, Christian Tyler. "DNA viruses and the cellular DNA repair machinery /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3175282.

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14

Leavitt, Markley Carl. "Bacteriophage T5 DNA polymerase relationships of DNA polymerases." Diss., The University of Arizona, 1990. http://hdl.handle.net/10150/185335.

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T5 DNA polymerase, a highly processive single polypeptide enzyme, and PRD1 DNA polymerase, a protein-primed DNA polymerase, have been analyzed for their primary structural features. The amino acid sequence of T5 DNA polymerase reveals a high degree of homology with DNA polymerase I (Pol I) of Escherichia coli and retains many of the amino acid residues which have been implicated in the 3'-5' exonuclease and DNA polymerase activities of that enzyme. Alignment with sequences of polymerase I and T7 DNA polymerase (family A polymerases) was used to identify regions possibly involved in the high processivity of this enzyme. Further amino acid sequence comparisons of T5 DNA polymerase with a large group of DNA polymerases (family B) previously shown to exhibit little similarity to Pol I, indicate certain sequence segments are shared among distantly related DNA polymerases. These shared regions have been implicated in the 3'-5' exonuclease function of Pol I which suggests that the proofreading domains of all these enzymes may be related. Mutations in these segments in T5 DNA polymerase (family A) and PRD1 DNA polymerase (family B) greatly decrease the exonuclease activity of these enzymes but leave the polymerase activities intact. Additionally, an exonuclease deficient T5 DNA polymerase is used in DNA sequencing reactions and yields consistent results with low background contamination on autoradiographs of polyacrylamide/urea gels. PRD1 mutants defective in 3 regions which are highly conserved among family B DNA polymerases, are deficient in DNA polymerase activity but retain exonuclease activity.

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15

Maul, Melanie. "DNA Photolyasen." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-109219.

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16

Günthner-Biller, Maria Margarete. "Immunstimulatorische DNA." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-128724.

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17

Mitchell, James Christopher. "DNA nanostructures." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.400206.

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18

Goodman, Russell Paul. "DNA tetrahedra." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433479.

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19

Green, Simon. "DNA nanomachines." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432563.

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20

Amos, Martyn. "DNA computation." Thesis, University of Warwick, 1997. http://wrap.warwick.ac.uk/4238/.

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This is the first ever doctoral thesis in the field of DNA computation. The field has its roots in the late 1950s, when the Nobel laureate Richard Feynman first introduced the concept of computing at a molecular level. Feynman's visionary idea was only realised in 1994, when Leonard Adleman performed the first ever truly molecular-level computation using DNA combined with the tools and techniques of molecular biology. Since Adleman reported the results of his seminal experiment, there has been a flurry of interest in the idea of using DNA to perform computations. The potential benefits of using this particular molecule are enormous: by harnessing the massive inherent parallelism of performing concurrent operations on trillions of strands, we may one day be able to compress the power of today's supercomputer into a single test tube. However, if we compare the development of DNA-based computers to that of their silicon counterparts, it is clear that molecular computers are still in their infancy. Current work in this area is concerned mainly with abstract models of computation and simple proof-of-principle experiments. The goal of this thesis is to present our contribution to the field, placing it in the context of the existing body of work. Our new results concern a general model of DNA computation, an error-resistant implementation of the model, experimental investigation of the implementation and an assessment of the complexity and viability of DNA computations. We begin by recounting the historical background to the search for the structure of DNA. By providing a detailed description of this molecule and the operations we may perform on it, we lay down the foundations for subsequent chapters. We then describe the basic models of DNA computation that have been proposed to date. In particular, we describe our parallel filtering model, which is the first to provide a general framework for the elegant expression of algorithms for NP-complete problems. The implementation of such abstract models is crucial to their success. Previous experiments that have been carried out suffer from their reliance on various error-prone laboratory techniques. We show for the first time how one particular operation, hybridisation extraction, may be replaced by an error-resistant enzymatic separation technique. We also describe a novel solution read-out procedure that utilizes cloning, and is sufficiently general to allow it to be used in any experimental implementation. The results of preliminary tests of these techniques are then reported. Several important conclusions are to be drawn from these investigations, and we report these in the hope that they will provide useful experimental guidance in the future. The final contribution of this thesis is a rigorous consideration of the complexity and viability of DNA computations. We argue that existing analyses of models of DNA computation are flawed and unrealistic. In order to obtain more realistic measures of the time and space complexity of DNA computations we describe a new strong model, and reassess previously described algorithms within it. We review the search for "killer applications": applications of DNA computing that will establish the superiority of this paradigm within a certain domain. We conclude the thesis with a description of several open problems in the field of DNA computation.

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21

Chang, Hung Yuan. "Bridge DNA." Thesis, Rochester Institute of Technology, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10822889.

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This thesis work centers on the relationship between bridge structure, construction methods and timberwork, coming from the processes of design and manufacturing. In this thesis, I intend to discover and develop different characteristics of different structures and materials and create works that are visually powerful using different visual languages. I began to learn about bridge design after I started working full time after graduating from university. During that period I was involved in the creation of several bridge designs and obtained experience as a builder. The bridge that I helped to design and build during that period is still one of the largest and most important works for me. Since the experience was so influential I planned to apply that exceptional experience in designing furniture and creating unique works in my graduate program.

In my work, the process of research and design is as follows: 1. Start with the foundations of bridge structure. 2. Ensure reasonable structure is embedded into design. 3. Receive feedback, determine problems and limitations. 4. Continue designing and find the best ways to settle problems and address limitations. 5. Develop structural forms and apply them to the next projects.

Through my thesis work, I carried out interactive creation through observing, investigating and probing the possibilities of applying different bridge structures to the building of furniture.

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22

Zwolak, Michael Philip. "DNA Electronics." Thesis, Virginia Tech, 2003. http://hdl.handle.net/10919/78135.

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DNA is a potential component in molecular electronics. To explore this end, there has been an incredible amount of research on how well DNA conducts and by what mechanism. There has also been a tremendous amount of research to find new uses for it in nanoscale electronics. DNA's self-assembly and recognition properties have found a unique place in this area. We predict, using a tight-binding model, that spin-dependent transport can be observed in short DNA molecules sandwiched between ferromagnetic contacts. In particular, we show that a DNA spin-valve can be realized with magnetoresistance values of as much as 26% for Ni and 16% for Fe contacts. Spin-dependent transport can broaden the possible applications of DNA as a component in molecular electronics and shed new light into the transport properties of this important biological molecule.
Master of Science

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23

Aparício, James Monteiro. "DNA symmetry." Master's thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/8627.

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Mestrado em Engenharia de Computadores e Telemática
A investigação do DNA tem sido uma das áreas de investigação mais exploradas no último século. Desde a sua primeira descrição até à primeira sequência completa do genoma humano muito foi descoberto, mas ainda estamos longe de o compreender completamente. Neste trabalho tentámos explorar a ordem até à qual se verifica a existência de simetria relevante em genomas, e para esse fim, usámos um conjunto de genomas de vários organismos. Tentámos encontar relação entre os vários genomas através das características de simetria. Foram analisados três tipos de simetria: simetria inversa, simetria reversa e simetria complementar. Usámos, ainda, uma nova medida para classificar a simetria: a proporção de pares equivalentes. A natureza das operações envolvidas, o tamanho da memória e a eficiência temporal são factores a ter em conta aquando do desenvolvimento de ferramentas computacionais. Várias soluções foram exploradas tendo como objectivo minimizar a memória utilizada e minimizar o tempo de execução. Confirma-se uma tendência para a existência de simetria inversa no conjunto dos genomas usados e observou-se que existe associação entre os resultados das medidas de simetria e o tamanho dos genomas.
DNA research has been one of the most explored areas in the last century. From its first description to the first complete human genome sequence a lot has been discovered, but we are still far from fully understanding it. With this work we tried to find until which order is relevant symmetry found in genomes and for that purpose, we used several genomes of different organisms. We tried to find a relation between the various genomes by analysing their symmetry characteristics. Three types of symmetry were analysed: complementary symmetry, reverse symmetry, and inverted symmetry. Also, a new symmetry measure was used: the proportion of equivalent pairs. The nature of the operations involved, memory space and time efficiency are important factors to be considered when developing computational tools. A few different solutions are explored in order to minimize memory allocation and minimize runtimes. This work confirms a tendency for the inverted symmetry in the set of genomes used and it was also observed an association between the symmetry measure results and the size of the genomes.

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24

Nucci, André Luis Carrilho. "DNA arquitetônico." reponame:Repositório Institucional da UFSC, 2012. http://repositorio.ufsc.br/xmlui/handle/123456789/100891.

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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-graduação em Arquitetura e Urbanismo
Made available in DSpace on 2013-06-25T23:38:38Z (GMT). No. of bitstreams: 1 313280.pdf: 11205896 bytes, checksum: 0930b6dcc0221ca4f7b13aed4dddc372 (MD5)
Ao longo do tempo se produziu um estoque de artefatos arquitetônicos, e para a preservação dos mesmos já existem diretrizes, porém ficam aos cuidados dessas, somente poucos exemplares responsáveis por manter a memoria cultural, mais do que ser essa representação histórica, a arquitetura deve cumprir um papel de servir a humanidade de espaços uteis esses podendo ser preservados e disponibilizados ao uso por tempo indeterminado, visto os cuidados dados ao longo da vida.A genética promove uma evolução das estruturas orgânicas, pensando nessa maneira de perpetuar é que se faz uma analogia com a memética uma ciência nova que promove a evolução cultural, procurando perpetuar o caráter intangível de toda e qualquer estrutura, o DNA então se coloca como o código de elementos que determinam as características tanto dessas estruturas orgânicas como de qualquer outra ideia, se propondo nessa pesquisa como uma metáfora de conceitos e imagens que representem um partido para se desenvolver trabalhos futuros que levem a arquitetura antiga como suporte.Propõe-se para a ciência de arquitetura a adaptação de uma metodologia de projeto do design para co-criar trabalhos que venham a salvaguardar as obras de arquitetura, não se resguardado somente a matéria, mas de toda dimensão espacial, desenvolve-se por fim neste trabalho uma validação da metodologia adaptada, diagnosticando um DNA do Espaço Arquitetônico para uma edificação de relevância para a sociedade.

Abstract : Over time a stock of architectural artifacts has been produced, and although preservation guidelines already exist, only a handful of those artifacts, responsible for maintaining cultural memory, are under their care. Rather than being just a historical representation, architecture should be valued in its role of serving humanity with useful spaces which can be preserved and made available for use indefinitely, if appropriate care is taken throughout an artifacts' life. Genetics promote an evolution of organic structures, and in thinking about that perpetuation aspect we can draw an analogy with memetics, a new science that promotes cultural evolution, seeking to perpetuate the intangible nature of any structure. In that context, the DNA is posed as code elements that determine the characteristics of not only these organic structures ut also any other idea, being, in this research, used as a metaphor for the concepts and images which are the basis to develop future work supported in traditional architecture. This research proposes that architectural sciences adapt a design methodology in order to cocreate solutions that will safeguard architectural works, not only in the material, but in every spatial dimension and, for that purpose, we have developed a validation study of the adapted methodology by diagnosing the DNA of Architectural Space for a building of relevance to society.

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25

Pospiech, H. (Helmut). "The role of DNA polymerases, in particular DNA polymerase ε in DNA repair and replication". Doctoral thesis, University of Oulu, 2002. http://urn.fi/urn:isbn:9514266692.

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Abstract Analysis of the primary structure of DNA polymerase ε B subunit defined similarities to B subunits of eukaryotic DNA polymerases α, δ and ε as well as the small subunits of DNA polymerase DI of Euryarchaeota. Multiple sequence alignment of these proteins revealed the presence of 12 conserved motifs and defined a novel protein superfamily. The members of the B subunit family share a common domain architecture, suggesting a similar fold, and arguing for a conserved function among these proteins. The contribution of human DNA polymerase ε to nuclear DNA replication was studied using the antibody K18 that specifically inhibits the activity of this enzyme in vitro. This antibody significantly inhibited DNA synthesis both when microinjected into nuclei of exponentially growing human fibroblasts and in isolated HeLa cell nuclei, but did not inhibit SV40 DNA replication in vitro. These results suggest that the human DNA polymerase ε contributes substantially to the replicative synthesis of DNA and emphasises the differences between cellular replication and viral model systems. The human DNA polymerases ε and δ were found capable of gap-filling DNA synthesis during nucleotide excision repair in vitro. Both enzymes required PCNA and the clamp loader RFC, and in addition, polymerase δ required Fen-1 to prevent excessive displacement synthesis. Nucleotide excision repair of a defined DNA lesion was completely reconstituted utilising largely recombinant proteins, only ligase I and DNA polymerases δ and ε provided as highly purified human enzymes. This system was also utilised to study the role of the transcription factor II H during repair. Human non-homologous end joining of model substrates with different DNA end configurations was studied in HeLa cell extracts. This process depended partially on DNA synthesis as an aphidicolin-dependent DNA polymerase was required for the formation of a subset of end joining products. Experiments with neutralising antibodies reveal that DNA polymerase α but not DNA polymerases β or ε, may represent this DNA polymerase activity. Our results indicate that DNA synthesis contributes to the stability of DNA ends, and influences both the efficiency and outcome of the end joining event. Furthermore, our results suggest a minor role of PCNA in non-homologous end joining.

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26

Boccongelli, Marina. "Etude expérimentale de la stabilité, sélectivité d'appariement et dynamique d'oligonucléotides DNA-DNA et LNA-DNA." Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210549.

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Le traitement et le diagnostic de maladies d'origine génétique suscite un grand intérêt à l'heure actuelle. De par leur spécificité d'appariement avec les acides nucléiques, les oligonucléotides possèdent un grand potentiel dans ce domaine. Ils se heurtent toutefois à des limitations majeures, dont leur faible stabilité en milieu physiologique et la difficulté qu'ils ont à franchir les membranes biologiques. De nombreuses équipes de recherche s'intéressent, afin de pallier ces limitations, à la conception et à la synthèse d'oligonucléotides chimiquement modifiés. Parmi ceux-ci, les Locked Nucleic Acids (LNA), présentant une modification qui consiste en l'insertion d'un pont −O−CH2− entre l'atome C2' et l'atome C4' du sucre, constituent une famille qui semble posséder les propriétés requises. Ils sont considérés comme des candidats très prometteurs en tant qu’agents thérapeutiques et qu’outils de diagnostic du génome. La caractérisation de la stabilité et de la sélectivité d'appariement entre les LNA et les acides nucléiques naturels est, dans ce contexte, important.

Dans ce travail, nous avons étudié la stabilité, la sélectivité d'appariement ainsi que la dynamique de la structure double brin d'un oligonucléotide hybride LNA-DNA, et nous avons comparé ces propriétés à celles d'un oligonucléotide DNA-DNA de même séquence. Ce dernier est constitué de 11 paires de bases formées par l'appariement du brin 5'-GCGTGTGTGCG-3' avec le brin 3'-CGCACACACGC-5'. Dans le cas de l'hybride, les nucléotides du second brin sont tous remplacés par des LNA.

La stabilité a été étudiée expérimentalement par différentes techniques :spectroscopie d'absorption UV, calorimétrie différentielle à balayage, résonance magnétique nucléaire et calorimétrie à titrage isotherme. Ces études montrent que la stabilité du duplexe hybride est plus importante que celle du naturel, et que ce phénomène s'explique par un terme entropique plus favorable pour la formation du duplexe LNA-DNA que pour la formation du duplexe DNA-DNA.

La sélectivité d'appariement a été étudiée en comparant la stabilité des deux oligonucléotides étudiés avec celle d'oligonucléotides présentant un mésappariement dans la séquence. Nos résultats montrent que la sélectivité d'appariement du brin LNA n'est pas significativement différente de celle du brin DNA. Ce résultat ne doit cependant pas être généralisé car nous n'avons testé qu'une position centrale pour le mésappariement.

L'étude de la dynamique de la structure des oligonucléotides a été effectuée par RMN et porte sur la caractérisation de la cinétique de l'ouverture individuelle des paires de bases. Nous observons que la durée de vie de l'état fermé des paires de bases G-C est supérieure dans l'oligonucléotide LNA-DNA, tandis que l'état fermé des paires A-T semble posséder une durée de vie supérieure dans l'oligonucléotide DNA-DNA.

Au cours de ce travail de thèse nous avons pu caractériser les facteurs énergétiques à la base de la stabilité accrue des oligonucléotides chimiquement modifiés de type LNA. Nous avons montré que leur sélectivité d’appariement n’est pas toujours supérieure à celle des oligonucléotides naturels et dépend des séquences impliquées. Enfin, nous avons mis en évidence les différences entre la dynamique de la structure d’un oligonucléotide possédant des LNA et celle d’un duplexe DNA.
Doctorat en Sciences de l'ingénieur
info:eu-repo/semantics/nonPublished

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27

Aldaye, Faisal A. 1979. "Supramolecular DNA nanotechnology : discrete nanoparticle organization, three-dimensional DNA construction, and molecule templated DNA assembly." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115668.

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The field of structural DNA nanotechnology utilizes DNA's powerful base-pairing molecular recognition criteria to help solve real challenges facing researchers in material science and nanotechnology, some of which include synthesis, sensing, catalysis, delivery, storage, optics, electronics, and scaffolding. In it, DNA is stripped away from any of its preconceived biological roles, and is treated as a powerful synthetic polymer. A subarea of research that our group has recently termed supramolecular DNA nanotechnology is emerging, and is proving to be a powerful complement to some of the already established rules of structural DNA nanotechnology. The work within this thesis falls under the umbrella of supramolecular DNA nanotechnology, and can conceptually be divided into three parts. (1) The first deals with the problem of discrete nanopartic1e organization. In it we present an approach for the facile and economical access to libraries of discrete nanoparticle assemblies that are addressable and switchable post-assembly. (2) The second deals with the synthesis of three-dimensional DNA assemblies. In it we present an approach for the facile construction of discrete three-dimensional DNA cages that can be structurally oscillated between pre-defined lengths, and adapt this approach to generate geometrically well-defined DNA columns of modular stiffness. (3) The last part deals with the use of small molecules to reprogram the assembly behavior of DNA. In it we use molecules to address the issue of error-correction, during and after the assembly process, and to facilitate the synthesis of "higher-order" DNA helices composed of more than two DNA strands. This work collectively offers a set of simple solutions to some of the bigger challenges currently facing researchers in DNA nanotechnology, and provides a snapshot of what is to be expected from tehe emerging discipline that is supramolecular DNA nanotechnology.

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28

Zhang, Jianhua. "Restriction fragment length polymorphism analysis of chloroplast DNA, mitochondrial DNA, and ribosomal DNA in turfgrasses." Diss., This resource online, 1994. http://scholar.lib.vt.edu/theses/available/etd-06062008-170748/.

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29

Rebelo, Adriana. "Probing Mitochondrial DNA Structure with Mitochondria-Targeted DNA Methyltransferases." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/344.

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The mitochondria contain their own genome, which is organized in a dynamic high-order nucleoid structure consisting of several copies of mitochondrial DNA (mtDNA) molecules associated with proteins. The mitochondrial nucleoids are the units of mtDNA inheritance, and are the sites of mtDNA transcription, replication and maintenance. Therefore, the integrity of mitochondrial nucleoids is a key determinant of mitochondrial metabolism and the bioenergetic state of the cell. Deciphering the interaction of mtDNA with proteins in nucleoprotein complexes is fundamental to understand the mechanisms of mtDNA segregation leading to mitochondrial dysfunction and to develop therapies to treat diseases associated with mtDNA mutations. The work presented in this dissertation provides essential insights into the dynamics of mtDNA interaction with nucleoid proteins. In order to unveil the organization of the mitochondrial genome, we have mapped major regulatory regions of the mtDNA in vivo using mitochondrial-targeted DNA methyltransferases. In chapter 2, we have demonstrated that DNA methyltranferases are powerful tools in probing mtDNA-protein interactions in living cells. The DNA methyltransferases' accessibility to their cognate sites in the mtDNA is negatively correlated with the frequency and binding strength that protein factors occupy a specific site. Our results show that the transcription termination region (TERM) within the tRNALeu(UUR) gene is consistently and strongly protected from methylation, suggesting frequent and high affinity binding of mTERF1 (mitochondrial transcription termination factor 1). DNA methyltransferases have also been shown to be effective in detecting changes in mitochondrial nucleoid architecture due to nucleoid remodeling. We were able to determine changes in the packaging state of mitochondrial nucleoids by monitoring changes in mtDNA accessibility. The impact of altered levels of major nucleoid proteins was assessed by monitoring changes in mtDNA methylation pattern. We observed a more condensed nucleoid state causing a decrease in mtDNA methylation when the levels of the mitochondrial transcription factor A (TFAM) were altered. Changes in mtDNA methylation pattern were also evident when cells were treated with ethidium bromide (EtBr) and hydrogen peroxide. The mtDNA nucleoids adopted a less compact state during rapid mtDNA replication after EtBr treatment. In contrast, we observed a more compact mtDNA, less accessible to DNA methyltransferase after hydrogen peroxide treatment. Our results indicate that mitochondrial nucleoids are not static, but are constantly been modulated in response to factors that affect the nucleoid environment. In chapter 3, we identified the in vivo DNA binding sites of major transcription regulatory proteins, TFAM and mTERF3 using a targeted gene methylation (TAGM) strategy. In this approach, the mtDNA binding protein is fused to a DNA methyltransferase as an attempt to selectively methylate the sites adjacent to the protein target DNA region. Knowledge on how proteins interact with the mtDNA in high-order structures, which function as a mitochondrial genetic unit, will help elucidate the segregation and accumulation of mutated mtDNA in diseased tissues.

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30

Sando, Shinsuke. "RATIONAL DESIGN OF DNA-BINDING MOLECULES AND DNA PHOTOCLEAVERS." 京都大学 (Kyoto University), 2001. http://hdl.handle.net/2433/150700.

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31

Protozanova, Ekaterina. "Physicochemical characterization of multistranded DNA assemblies, DNA frayed wires." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq53831.pdf.

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32

Peeva, Viktoriya [Verfasser]. "Rearranged DNA in mitochondrial DNA maintenance disorders / Viktoriya Peeva." Bonn : Universitäts- und Landesbibliothek Bonn, 2015. http://d-nb.info/1077289669/34.

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33

Rungsardthong, Uracha. "Physicochemical evaluation of polymer-DNA complexes for DNA delivery." Thesis, University of Nottingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394855.

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34

Lever, Catherine. "The study of DNA-DNA interactions using modified oligonucleotides." Thesis, University of Liverpool, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317140.

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35

Mackenney, Victoria Jane. "Human DNA ligase I in DNA replication and repair." Thesis, King's College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267515.

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36

Minchell, Nicola E. "DNA topological stress during DNA replication in Saccharomyces cerevisiae." Thesis, University of Sussex, 2019. http://sro.sussex.ac.uk/id/eprint/81222/.

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DNA topological stress impedes normal DNA replication. If topological stress is allowed to build up in front of the replication fork, the fork rotates to overcome the stress, leading to formation of DNA pre-catenanes. The formation of DNA pre-catenanes is therefore a marker of DNA topological stress. In this study, I have examined how transcription linked DNA topological stress impacts on fork rotation and on endogenous DNA damage. Transcription, similar to replication, affects the topology of the DNA; and collision between the two machineries is likely to lead to high levels of DNA topological stress. I found that the frequency of fork rotation during DNA replication, increases with the number of genes present on a plasmid. Interestingly, I also found that this increase in pre-catenation is dependent on the cohesin complex. Cohesin and transcription are known to be linked, as transcription leads to the translocation of cohesin along budding yeast DNA away from its loading sites. Cohesin plays a major role in establishing chromosomal structure, influencing gene expression and genetic inheritance. In this work, I have analysed the relationship between cohesin and the generation of topological stress and found that topological stress associated with cohesin can lead to DNA replication stress and DNA damage.

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37

Gould, Poppy Aeron. "The role of DNA repair in DNA methylation dynamics." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/274360.

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The mammalian epigenome is globally reprogrammed at two stages of development; this involves the erasure and re-establishment of DNA methylation by both passive and active mechanisms, including DNA repair pathways, and occurs concurrently with an increase in developmental potency. In addition to Uhrf1 and the Tet enzymes, the interplay between activation induced cytidine deaminase (AID) and the DNA repair machinery has been implicated in epigenetic reprogramming of various in vivo and in vitro systems including mouse primordial germ cells, zygotes and induced pluripotent stem cells. AID deaminates cytosine to uracil and can also deaminate methylcytosine, whereas the primary role of UNG is to maintain the integrity of the genome through erasure of uracil. In this thesis, I have aimed to investigate the role of DNA repair in demethylation. To do this I have focused on the specific role of AID and UNG in the demethylation of a static system – primed serum ESCs and a dynamic system – serum to 2i (naïve) to epiblast-like ES cells. As the role of both AID and UNG involves genomic uracil, the central theme of my thesis is the impact of accumulation of uracil on DNA methylation levels in the genome. Therefore, my first aim was to develop a quantitative method to detect low levels of genomic uracil in DNA firstly, by mass spectrometry and secondly, by whole genome sequencing. In Chapter Three, I show that the impact of deamination during DNA preparation can be minimised, such that the level of genomic ESC uracil can be accurately determined as around 12,000 uracil per genome and that, as anticipated, Ung null ESCs have almost twice the genomic uracil content of wildtype ESCs. Secondly, I address the main question which is the impact of uracil accumulation on methylation levels. In order to do this, I generate two cell lines: Ung knockout and Aid over expressing, both of which should result in an increase in genomic uracil. I demonstrate that while over expression of Aid stimulates demethylation in static system and in a dynamic demethylating system, the impact of Ung knockout is less clear. In (static) serum ESCs, loss of Ung results in hypomethylation however, in order to transition to 2i (naïve) ESCs, a process which involves demethylation of the genome, it appears the Ung is required as loss of this gene inhibits proper demethylation. As such, I conclude that UNG-mediated DNA repair functions alongside passive demethylation, by reduction of UHRF1 levels, to demethylate 2i ESCs. To probe the mechanism by which accumulation of uracil in the genome alters methylation levels, I investigate the impact of Ung KO and Aid OE on global levels of DNA damage. I show that both cell lines have a greater incidence of double strand breaks compared to a wild type cell line, and accordingly, upregulate their DNA damage response pathway and the expression of certain repair genes. I suggest that increasing genomic levels of uracil causes genomic instability and that DNA demethylation occurs as a consequence of the repair of extensive DNA damage. More broadly, I suggest that ESCs are uniquely poised, due to their heightened DNA damage response, to use uracil as an intermediate of DNA demethylation. Interestingly, I also note that the biological impact on serum ESCs of loss of Ung appears to be an increase in pluripotency.

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38

Neaves, Kelly Jane. "Atomic force microscopy of DNA and DNA-protein constructs." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608615.

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39

Palm, Nathalie. "DNA-bevisning : om värdering av DNA-spår i brottmål." Thesis, Stockholms universitet, Juridiska institutionen, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-127740.

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40

Ouldridge, Thomas E. "Coarse-grained modelling of DNA and DNA self-assembly." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:b2415bb2-7975-4f59-b5e2-8c022b4a3719.

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In this thesis I present a novel coarse-grained model of deoxyribonucleic acid (DNA). The model represents single-stranded DNA as a chain of rigid nucleotides, and includes potentials to represent chain connectivity, excluded volume, hydrogen-bonding and base stacking interactions. The parameterization of these interactions is justified by comparing the model's representation of a range of physical phenomena to experimental data. In particular, the geometrical structure and elastic moduli of duplex DNA, and the flexibility of single-stranded DNA, are shown to be physically reasonable. Additionally, the thermodynamics of single-stranded stacking, duplex hybridization, hairpin formation and more complex motifs are shown to agree well with experimental data. The model is optimized for capturing the thermodynamic and mechanical changes associated with duplex formation from single strands. Considerable attention is therefore given to ensuring that single-stranded DNA behaves physically, an approach which differs from previous attempts to model DNA. As a result, the model is the first in which an explicit stacking transition is present in single strands, and also the only coarse-grained model to date to capture both hairpin formation within a single strand and duplex formation between strands. The scope of the model is demonstrated by simulating DNA tweezers, an iconic nanodevice -- the first time that coarse-grained modelling has been applied to dynamic DNA nanotechnology. The simulations suggest that branch migration during toehold-mediated strand displacement -- a central feature of many nanomachines -- does not have a flat free-energy profile, as is generally assumed. This finding may help to explain the observed dependence of displacement rate on toehold length. Finally, the operation of a two-footed DNA walker on a single-stranded DNA track is considered. The model suggests that several aspects of the walker will reduce its efficiency, including a tendency to bind to an undesired site on the track. Several design modifications are suggested to improve the operation of the walker.

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41

Isoz, Isabelle. "Role of yeast DNA polymerase epsilon during DNA replication." Doctoral thesis, Umeå : Umeå University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1932.

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42

Punchihewa, Chandanamalie. "DNA and DNA-Interacting Proteins as Anticancer Drug Targets." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/194379.

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DNA is both the oldest and newest of targets for cancer therapy. While it is already being targeted by many anticancer drugs in the clinic, the development of sequence-specific DNA binders has brought it back to the limelight as a valuable anticancer drug target.My studies on DNA interacting agents was initiated with the DNA intercalator campotothecin, and also included topoisomerase I enzyme. I have evaluated the structure of topoisomerase I C-terminal domain that consists of the active site tyrosine. My data indicate that this domain exists in a molten globule conformation with a fluctuating tertiary structure. These fluctuations are suggested to be important in interaction with the topoisomerase I core domain and DNA. I have also evaluated the DNA interactions of the camptothecin analogue homocamptothecin and have determined that homocamptothecin intercalate with DNA in the absence of topoisomerase I, and that such intercalation results in its lactone stabilization. Subsequently, the mechanism of topoisomerase I mediated inhibition of HIF-1 by camptothecin was explored. I have shown that camptothecin stimulate topoisomerase I cleavage complex formation in the HIF-1 binding site, which is suggested to prevent the DNA binding of HIF-1.The second part of this study was focused on understanding the mechanism of action of another DNA binder, XR5944. Designed as a dual topoisomerase inhibitor, XR5944 was subsequently shown to have a different mechanism of action - inhibition of trancription. The NMR structural analysis, in our lab, of the drug-DNA complex showed that XR5944 bis-intercalate with DNA, while binding in the DNA major groove. Driven by these combined interaction modes, XR5944 is shown to inhibit the DNA binding and the subsequent transcriptional activity of specific transcription factors such as estrogen receptors and AP-1, which are overexpressed in certain cancers.Finally, I have analyzed G-quadruplex structures formed by telomeric DNA. The formation and stabilization of DNA G-quadruplexes in the human telomeric sequence have been shown to inhibit the activity of telomerase. Thus the telomeric DNA G-quadruplex has been considered as an attractive anticancer drug target. Telomeric DNA forms multiple G-quadruplex conformations, and my data reveal the conformations of the major G-quadruplexes formed by human telomeres.

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43

Lückerath, Thorsten [Verfasser]. "RAFT polymerization from DNA for DNA-polymer conjugates and higher-ordered DNA-polymer architectures / Thorsten Lückerath." Ulm : Universität Ulm, 2021. http://d-nb.info/1229993983/34.

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44

Li, Jian. "Mechanism of DNA Homologous Recombination through Studies of DNA Sliding Clamps, Clamp Loaders, and DNA Polymerases." Ohio University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1374835449.

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45

Manetto, Antonio. "I-Modified Nucleosides as DNA-Sugar Centered Radical Precursors II-DNA Excess Electron Transfer Studies III-A new Direct DNA Detection Method: DNA Photography." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-83988.

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46

Tsusaka, Takeshi. "Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation." Kyoto University, 2018. http://hdl.handle.net/2433/232305.

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47

Amato, Nicholas J. "Impact of DNA Structure and Aeropyrum pernix Single-Strand DNA Binding Protein on Oxidative Damage to DNA." University of Toledo / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1372296254.

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48

Luo, Dan. "Novel crosslinking technologies to assess protein-DNA binding and DNA-DNA complexes for gene delivery and expression." The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1114436532.

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49

Sherrer, Shanen Michelle. "Mutagenic and Kinetic Effects of Various DNA Lesions on DNA Polymerization Catalyzed by Y-Family DNA Polymerases." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1313178275.

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50

Luo, Dan. "Novel crosslinking technologies to assess protein-DNA binding and DNA-DNA complexes for gene delivery and expression /." Connect to resource, 1998. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1114436532.

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Дисертації з теми "DNA"

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