Structural analysis of base mispairing in DNA containing oxidative guanine lesion

Open Physics ◽  
2007 ◽  
Vol 5 (1) ◽  
Author(s):  
Hirofumi Fujimoto ◽  
Miroslav Pinak ◽  
Toshiyuki Nemoto ◽  
Juraj Bunta
Keyword(s):  
Base Pair ◽  
Dna Bases ◽  
Pyrimidine Base ◽  
Normal Bases ◽  
Dna Molecule ◽  
Molecular Dynamics Methods ◽  
Opposite Strand ◽  
Base Mispairing ◽  
The Impact ◽  
Anti Form

AbstractClassical molecular dynamics methods were used to analyze the importance of 8-oxoguanine (8-oxoG) pairing with other DNA bases in order to determine the impact of oxidative guanine lesions on DNA structure. Six lesioned molecules, each containing 8-oxoG mispaired with one of the four normal bases on the the opposite strand at the center of 40-mer DNA, and one non-damaged DNA molecule, were simulated for 2 nanoseconds of real time. The 8-oxoG lesioned bases were found to incorporate opposite all normal bases. There are observed conformational and energetical differences among these parings. 8-oxoG in anti-form creates firm hydrogen bonds with cytosine and this bonding has a strong attractive electrostatic interaction energy similar to that of a native base pair-guanine to cytosine. Meanwhile, it does not form a stable base pair with purine bases (adenine and guanine) nor with the pyrimidine base thymine. On the other hand, the 8-oxoG in syn-form was found to pair with adenine.

scholarly journals Halogen-Bonded Guanine Base Pairs, Quartets and Ribbons

2020 ◽  
Vol 21 (18) ◽  
pp. 6571
Author(s):  
Nicholas J. Thornton ◽  
Tanja van Mourik
Keyword(s):  
Base Pair ◽  
Halogen Bond ◽  
Halogen Bonding ◽  
Dna Bases ◽  
Halogen Bonds ◽  
Base Pairs ◽  
Rich Diversity ◽  
Different Types ◽  
Guanine Base ◽  
The Stability

Halogen bonding is studied in different structures consisting of halogenated guanine DNA bases, including the Hoogsteen guanine–guanine base pair, two different types of guanine ribbons (R-I and R-II) consisting of two or three monomers, and guanine quartets. In the halogenated base pairs (except the Cl-base pair, which has a very non-planar structure with no halogen bonds) and R-I ribbons (except the At trimer), the potential N-X•••O interaction is sacrificed to optimise the N-X•••N halogen bond. In the At trimer, the astatines originally bonded to N1 in the halogen bond donating guanines have moved to the adjacent O6 atom, enabling O-At•••N, N-At•••O, and N-At•••At halogen bonds. The brominated and chlorinated R-II trimers contain two N-X•••N and two N-X•••O halogen bonds, whereas in the iodinated and astatinated trimers, one of the N-X•••N halogen bonds is lost. The corresponding R-II dimers keep the same halogen bond patterns. The G-quartets display a rich diversity of symmetries and halogen bond patterns, including N-X•••N, N-X•••O, N-X•••X, O-X•••X, and O-X•••O halogen bonds (the latter two facilitated by the transfer of halogens from N1 to O6). In general, halogenation decreases the stability of the structures. However, the stability increases with the increasing atomic number of the halogen, and the At-doped R-I trimer and the three most stable At-doped quartets are more stable than their hydrogenated counterparts. Significant deviations from linearity are found for some of the halogen bonds (with halogen bond angles around 150°).

DNA Base Identification by Electron Microscopy

2012 ◽  
Vol 18 (5) ◽  
pp. 1049-1053 ◽  
Author(s):  
David C. Bell ◽  
W. Kelley Thomas ◽  
Katelyn M. Murtagh ◽  
Cheryl A. Dionne ◽  
Adam C. Graham ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Base Pair ◽  
Heavy Atom ◽  
Genomic Research ◽  
Biological Research ◽  
Template Molecule ◽  
Dna Molecules ◽  
Base Pairs ◽  
Dna Molecule ◽  
Dna Base

AbstractAdvances in DNA sequencing, based on fluorescent microscopy, have transformed many areas of biological research. However, only relatively short molecules can be sequenced by these technologies. Dramatic improvements in genomic research will require accurate sequencing of long (>10,000 base-pairs), intact DNA molecules. Our approach directly visualizes the sequence of DNA molecules using electron microscopy. This report represents the first identification of DNA base pairs within intact DNA molecules by electron microscopy. By enzymatically incorporating modified bases, which contain atoms of increased atomic number, direct visualization and identification of individually labeled bases within a synthetic 3,272 base-pair DNA molecule and a 7,249 base-pair viral genome have been accomplished. This proof of principle is made possible by the use of a dUTP nucleotide, substituted with a single mercury atom attached to the nitrogenous base. One of these contrast-enhanced, heavy-atom-labeled bases is paired with each adenosine base in the template molecule and then built into a double-stranded DNA molecule by a template-directed DNA polymerase enzyme. This modification is small enough to allow very long molecules with labels at each A-U position. Image contrast is further enhanced by using annular dark-field scanning transmission electron microscopy (ADF-STEM). Further refinements to identify additional base types and more precisely determine the location of identified bases would allow full sequencing of long, intact DNA molecules, significantly improving the pace of complex genomic discoveries.

DNA spontaneous mutation and its role in the evolution of GC-content: assessing the impact of the genetic sequence

2015 ◽  
Vol 17 (12) ◽  
pp. 7754-7760 ◽  
Author(s):  
José P. Cerón-Carrasco ◽  
Denis Jacquemin
Keyword(s):  
Dna Sequence ◽  
Base Pair ◽  
Spontaneous Mutation ◽  
Gc Content ◽  
Genetic Sequence ◽  
The Impact

We use theoretical tools to investigate the possible role played by a DNA sequence in the base pair tautomerization phenomena.

Hook Formation of Electrically Driven DNA Collisions with Finite-Sized Obstacles

2003 ◽  
Vol 790 ◽  
Author(s):  
Greg C. Randall ◽  
Patrick S. Doyle
Keyword(s):  
Electric Field ◽  
Deborah Number ◽  
Local Electric Field ◽  
Electric Field Gradients ◽  
Size Dependent ◽  
Dna Molecule ◽  
Field Gradients ◽  
The Impact ◽  
Single Dna Molecule ◽  
Comprehensive Study

ABSTRACTWe present a comprehensive study of the hooking mechanism of a single DNA molecule in electrophoretic motion colliding with a single microfabricated obstacle. During a collision, DNA impacts an obstacle and deforms. The impact conditions dictate whether this collision results in a “roll-off” event or “hooking” event. Our objective is to better understand the physics of a collision. Specifically, we note that a finite-sized insulating obstacle induces local electric field gradients that can enhance the size-dependent hooking probability. We validate that the hooking mechanism is analogous to a polymer in a transient, non-homogeneous elongational field with a strength characterized by the Deborah number, De. We then show that hook formation increases with De for finite-sized obstacles in the regime De<40.

Pyrimidine · pyrimidine base-pair mismatches in DNA

1988 ◽  
Vol 202 (1) ◽  
pp. 139-155 ◽  
Author(s):  
Michael Kouchakdjian ◽  
Benjamin F.L. Li ◽  
Peter F. Swann ◽  
Dinshaw J. Patel
Keyword(s):  
Base Pair ◽  
Pyrimidine Base

scholarly journals Intramolecular dynamics of single molecules in free diffusion

2017 ◽  
Author(s):  
Charles Limouse ◽  
Jason C. Bell ◽  
Colin J. Fuller ◽  
Aaron F. Straight ◽  
Hideo Mabuchi
Keyword(s):  
Single Molecule ◽  
Conformational Dynamics ◽  
Correlation Spectroscopy ◽  
Biomolecular Systems ◽  
Optimal Position ◽  
Biochemical Processes ◽  
Fluorescence Correlation ◽  
Dna Molecule ◽  
Feedback Scheme ◽  
The Impact

AbstractBiomolecular systems such as multiprotein complexes or biopolymers can span several tens to several hundreds of nanometers, but the dynamics of such “mesocale” molecules remain challenging to probe. We have developed a single-molecule technique that uses Tracking Fluorescence Correlation Spectroscopy (tFCS) to measure the conformation and dynamics of molecular assemblies specifically at the mesoscale level (~100-1000 nm). tFCS is non-perturbative, as molecules, which are tracked in real-time, are untethered and freely diffusing. To achieve sub-diffraction spatial resolution, we use a feedback scheme which allows us to maintain the molecule at an optimal position within the laser intensity gradient. We find that tFCS is sufficiently sensitive to measure the distance fluctuations between two sites within a DNA molecule separated by distances as short as 1000 bp. We demonstrate that tFCS detects changes in the compaction of reconstituted chromatin, and can assay transient protein mediated interactions between distant sites in an individual DNA molecule. Our measurements highlight the impact that tFCS can have in the study of a wide variety of biochemical processes involving mesoscale conformational dynamics.

scholarly journals A MUTATIONAL ANALYSIS OF THE TRIPLO-LETHAL REGION OF DROSOPHILA MELANOGASTER

Genetics ◽  
1979 ◽  
Vol 91 (3) ◽  
pp. 421-441 ◽  
Author(s):  
D O Keppy ◽  
R E Denell
Keyword(s):  
Salivary Gland ◽  
Base Pair ◽  
Mutational Analysis ◽  
Chromosome Region ◽  
Chromosome Analysis ◽  
Salivary Gland Chromosome ◽  
Exceptional Locus ◽  
Dna Base Pair ◽  
The Impact ◽  
Sensitive Behavior

ABSTRACT The extensive analysis of the impact of segmental aneuploidy by LINDSLEY et al. (1972) showed that there are relatively few haplo-lethal loci in the genome and that, with one exception, all loci are triplo-viable. The exceptional locus, which lies in salivary gland chromosome region 83D-E, is associated with lethality when present in either one or three doses in an otherwise diploid individual (DENEU 1976). The genetic nature of the phenomenon has been studied by examining the rates of induction, by ionizing radiation and chemical mutagens, of mutations affecting the dose-sensitive behavior. For both types of mutagens, the frequency of inactivation of the locus is relatively low, and a high proportion of such mutations is associated with chromosomal deficiencies. These data indicate that the locus is infrequently and perhaps never inactivated by a DNA base-pair substitution and thus that the triplo-lethal phenomenon is not associated with a "typical" structural gene. It is possible that the triplo-lethal locus is very small, is reiterated or otherwise complex or is functionally insensitive to base-pair substitutions. The result that all mutations that complement a duplication of the triplo-lethal locus are lethal in heterozygous combination with a normal third chromosome argues that triplo- and haplo-lethality are concomitants of the same phenomenon. Salivary gland chromosome analysis of newly induced deficiencies and duplications localizes the locus to 83D4,5-83E1,2, and further cytogenetic manipulation shows that the dose-sensitive behavior is independent of the position of the locus in the genome.

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