Conformational Changes in Nucleic Acids Modified by Chemical Carcinogens

2019 ◽  
pp. 59-94 ◽  
Author(s):  
D. Grunberger ◽  
I. B. Weinstein
2020 ◽  
Vol 48 (9) ◽  
pp. e49-e49 ◽  
Author(s):  
Shreya Ghosh ◽  
Matthew J Lawless ◽  
Hanna J Brubaker ◽  
Kevin Singewald ◽  
Michael R Kurpiewski ◽  
...  

Abstract Electron paramagnetic resonance (EPR) has become an important tool to probe conformational changes in nucleic acids. An array of EPR labels for nucleic acids are available, but they often come at the cost of long tethers, are dependent on the presence of a particular nucleotide or can be placed only at the termini. Site directed incorporation of Cu2+-chelated to a ligand, 2,2′dipicolylamine (DPA) is potentially an attractive strategy for site-specific, nucleotide independent Cu2+-labelling in DNA. To fully understand the potential of this label, we undertook a systematic and detailed analysis of the Cu2+-DPA motif using EPR and molecular dynamics (MD) simulations. We used continuous wave EPR experiments to characterize Cu2+ binding to DPA as well as optimize Cu2+ loading conditions. We performed double electron-electron resonance (DEER) experiments at two frequencies to elucidate orientational selectivity effects. Furthermore, comparison of DEER and MD simulated distance distributions reveal a remarkable agreement in the most probable distances. The results illustrate the efficacy of the Cu2+-DPA in reporting on DNA backbone conformations for sufficiently long base pair separations. This labelling strategy can serve as an important tool for probing conformational changes in DNA upon interaction with other macromolecules.


2001 ◽  
Vol 260 (2) ◽  
pp. 293-307 ◽  
Author(s):  
Jan Barciszewski ◽  
Janusz Jurczak ◽  
Sylwester Porowski ◽  
Thomas Specht ◽  
Volker A. Erdmann

Biochimie ◽  
1976 ◽  
Vol 58 (4) ◽  
pp. 395-402 ◽  
Author(s):  
Maurice Durand ◽  
Hanna N. Borazan ◽  
Jean-Claude Maurizot ◽  
Jean-Luc Dimicoli ◽  
Claude Hélène

2021 ◽  
pp. 76-78
Author(s):  
R.V. Moryachkov ◽  
◽  
P.A. Nikolaeva ◽  
V.A. Spiridonova ◽  
◽  
...  

The high potential of aptamers – specifi c molecular agents based on short single-stranded nucleic acids – makes high demands on the molecules under development for the effi ciency of interaction with target biomolecules. In this work, approaches are considered for studying the spatial structure of DNA aptamers in solution using various complementary methods, which make it possible to obtain a more complete picture of the formation of the structure and conformational changes, to track the interaction with the target protein, the tendency to oligomerization, and to characterize the spatial structure of both individual molecules and complexes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raffaele Brogna ◽  
Juezhu Fan ◽  
Harald Sieme ◽  
Willem F. Wolkers ◽  
Harriëtte Oldenhof

AbstractEven though dried sperm is not viable, it can be used for fertilization as long as its chromatin remains intact. In this study, we investigated drying- and temperature-induced conformational changes of nucleic acids and stallion sperm chromatin. Sperm was diluted in preservation formulations with and without sugar/albumin and subjected to convective drying at elevated temperatures on glass substrates. Accumulation of reactive oxygen species was studied during storage at different temperatures, and the sperm chromatin structure assay was used to assess DNA damage. Fourier transform infrared spectroscopy was used to identify dehydration and storage induced conformational changes in isolated DNA and sperm chromatin. Furthermore, hydrogen bonding in the preservation solutions associated with storage stability were investigated. Reactive oxygen species and DNA damage in dried sperm samples were found to accumulate with increasing storage temperature and storage duration. Non-reducing disaccharides (i.e., trehalose, sucrose) and albumin counteracted oxidative stress and preserved sperm chromatin during dried storage, whereas glucose increased DNA damage during storage. When sperm was dried in the presence of trehalose and albumin, no spectral changes were detected during storage at refrigeration temperatures, whereas under accelerated aging conditions, i.e., storage at 37 °C, spectral changes were detected indicating alterations in sperm chromatin structure.


Nanomaterials ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 681 ◽  
Author(s):  
Ryan C. Oliver ◽  
Lewis A. Rolband ◽  
Alanna M. Hutchinson-Lundy ◽  
Kirill A. Afonin ◽  
Joanna K. Krueger

Nucleic acid-based technologies are an emerging research focus area for pharmacological and biological studies because they are biocompatible and can be designed to produce a variety of scaffolds at the nanometer scale. The use of nucleic acids (ribonucleic acid (RNA) and/or deoxyribonucleic acid (DNA)) as building materials in programming the assemblies and their further functionalization has recently established a new exciting field of RNA and DNA nanotechnology, which have both already produced a variety of different functional nanostructures and nanodevices. It is evident that the resultant architectures require detailed structural and functional characterization and that a variety of technical approaches must be employed to promote the development of the emerging fields. Small-angle X-ray and neutron scattering (SAS) are structural characterization techniques that are well placed to determine the conformation of nucleic acid nanoparticles (NANPs) under varying solution conditions, thus allowing for the optimization of their design. SAS experiments provide information on the overall shapes and particle dimensions of macromolecules and are ideal for following conformational changes of the molecular ensemble as it behaves in solution. In addition, the inherent differences in the neutron scattering of nucleic acids, lipids, and proteins, as well as the different neutron scattering properties of the isotopes of hydrogen, combined with the ability to uniformly label biological macromolecules with deuterium, allow one to characterize the conformations and relative dispositions of the individual components within an assembly of biomolecules. This article will review the application of SAS methods and provide a summary of their successful utilization in the emerging field of NANP technology to date, as well as share our vision on its use in complementing a broad suite of structural characterization tools with some simulated results that have never been shared before.


2018 ◽  
Vol 16 (48) ◽  
pp. 9402-9408 ◽  
Author(s):  
Pan Li ◽  
Zhe Chen ◽  
Yishun Huang ◽  
Jing Li ◽  
Fan Xiao ◽  
...  

DNA-AIEgen hybrids show pH-responsive AIE effects induced by the conformational changes of DNA upon pH variation.


2020 ◽  
Vol 48 (11) ◽  
pp. e61-e61 ◽  
Author(s):  
Michela Zuffo ◽  
Aurélie Gandolfini ◽  
Brahim Heddi ◽  
Anton Granzhan

Abstract High-throughput investigation of structural diversity of nucleic acids is hampered by the lack of suitable label-free methods, combining fast and cheap experimental workflow with high information content. Here, we explore the use of intrinsic fluorescence emitted by nucleic acids for this scope. After a preliminary assessment of suitability of this phenomenon for tracking conformational changes of DNA, we examined steady-state emission spectra of an 89-membered set of oligonucleotides with reported conformation (G-quadruplexes (G4s), i-motifs, single- and double-strands) by means of multivariate analysis. Principal component analysis of emission spectra resulted in successful clustering of oligonucleotides into three corresponding conformational groups, without discrimination between single- and double-stranded structures. Linear discriminant analysis was exploited for the assessment of novel sequences, allowing the evaluation of their G4-forming propensity. Our method does not require any labeling agent or dye, avoiding the related bias, and can be utilized to screen novel sequences of interest in a high-throughput and cost-effective manner. In addition, we observed that left-handed (Z-) G4 structures were systematically more fluorescent than most other G4 structures, almost reaching the quantum yield of 5′-d[(G3T)3G3]-3′ (G3T, the most fluorescent G4 structure reported to date).


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