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2377 KiB

Open AccessArticle

by Pamela J. Perez, Nicolas Clauvelin, Michael A. Grosner, Andrew V. Colasanti and Wilma K. Olson

Int. J. Mol. Sci. 2014, 15(9), 15090-15108; https://doi.org/10.3390/ijms150915090 - 27 Aug 2014

Cited by 7 | Viewed by 7253

The looping of DNA provides a means of communication between sequentially distant genomic sites that operate in tandem to express, copy, and repair the information encoded in the DNA base sequence. The short loops implicated in the expression of bacterial genes suggest that [...] Read more.

The looping of DNA provides a means of communication between sequentially distant genomic sites that operate in tandem to express, copy, and repair the information encoded in the DNA base sequence. The short loops implicated in the expression of bacterial genes suggest that molecular factors other than the naturally stiff double helix are involved in bringing the interacting sites into close spatial proximity. New computational techniques that take direct account of the three-dimensional structures and fluctuations of protein and DNA allow us to examine the likely means of enhancing such communication. Here, we describe the application of these approaches to the looping of a 92 base-pair DNA segment between the headpieces of the tetrameric Escherichia coli Lac repressor protein. The distortions of the double helix induced by a second protein—the nonspecific nucleoid protein HU—increase the computed likelihood of looping by several orders of magnitude over that of DNA alone. Large-scale deformations of the repressor, sequence-dependent features in the DNA loop, and deformability of the DNA operators also enhance looping, although to lesser degrees. The correspondence between the predicted looping propensities and the ease of looping derived from gene-expression and single-molecule measurements lends credence to the derived structural picture. Full article

(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)

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1565 KiB

Open AccessArticle

Theoretical Study of the Transpore Velocity Control of Single-Stranded DNA

by Weixin Qian, Kentaro Doi, Satoshi Uehara, Kaito Morita and Satoyuki Kawano

Int. J. Mol. Sci. 2014, 15(8), 13817-13832; https://doi.org/10.3390/ijms150813817 - 11 Aug 2014

Cited by 13 | Viewed by 5722

Abstract

The electrokinetic transport dynamics of deoxyribonucleic acid (DNA) molecules have recently attracted significant attention in various fields of research. Our group is interested in the detailed examination of the behavior of DNA when confined in micro/nanofluidic channels. In the present study, the translocation [...] Read more.

The electrokinetic transport dynamics of deoxyribonucleic acid (DNA) molecules have recently attracted significant attention in various fields of research. Our group is interested in the detailed examination of the behavior of DNA when confined in micro/nanofluidic channels. In the present study, the translocation mechanism of a DNA-like polymer chain in a nanofluidic channel was investigated using Langevin dynamics simulations. A coarse-grained bead-spring model was developed to simulate the dynamics of a long polymer chain passing through a rectangular cross-section nanopore embedded in a nanochannel, under the influence of a nonuniform electric field. Varying the cross-sectional area of the nanopore was found to allow optimization of the translocation process through modification of the electric field in the flow channel, since a drastic drop in the electric potential at the nanopore was induced by changing the cross-section. Furthermore, the configuration of the polymer chain in the nanopore was observed to determine its translocation velocity. The competition between the strength of the electric field and confinement in the small pore produces various transport mechanisms and the results of this study thus represent a means of optimizing the design of nanofluidic devices for single molecule detection. Full article

(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)

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1234 KiB

Open AccessCommunication

DNA Break Mapping Reveals Topoisomerase II Activity Genome-Wide

by Laura Baranello, Fedor Kouzine, Damian Wojtowicz, Kairong Cui, Teresa M. Przytycka, Keji Zhao and David Levens

Int. J. Mol. Sci. 2014, 15(7), 13111-13122; https://doi.org/10.3390/ijms150713111 - 23 Jul 2014

Cited by 61 | Viewed by 9883

Abstract

Genomic DNA is under constant assault by endogenous and exogenous DNA damaging agents. DNA breakage can represent a major threat to genome integrity but can also be necessary for genome function. Here we present approaches to map DNA double-strand breaks (DSBs) and single-strand [...] Read more.

Genomic DNA is under constant assault by endogenous and exogenous DNA damaging agents. DNA breakage can represent a major threat to genome integrity but can also be necessary for genome function. Here we present approaches to map DNA double-strand breaks (DSBs) and single-strand breaks (SSBs) at the genome-wide scale by two methods called DSB- and SSB-Seq, respectively. We tested these methods in human colon cancer cells and validated the results using the Topoisomerase II (Top2)-poisoning agent etoposide (ETO). Our results show that the combination of ETO treatment with break-mapping techniques is a powerful method to elaborate the pattern of Top2 enzymatic activity across the genome. Full article

(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)

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1865 KiB

Open AccessArticle

Base Flip in DNA Studied by Molecular Dynamics Simulationsof Differently-Oxidized Forms of Methyl-Cytosine

by Mahdi Bagherpoor Helabad, Natalia Kanaan and Petra Imhof

Int. J. Mol. Sci. 2014, 15(7), 11799-11816; https://doi.org/10.3390/ijms150711799 - 03 Jul 2014

Cited by 7 | Viewed by 6996

Abstract

Distortions in the DNA sequence, such as damage or mispairs, are specifically recognized and processed by DNA repair enzymes. Many repair proteins and, in particular, glycosylases flip the target base out of the DNA helix into the enzyme’s active site. Our molecular dynamics [...] Read more.

Distortions in the DNA sequence, such as damage or mispairs, are specifically recognized and processed by DNA repair enzymes. Many repair proteins and, in particular, glycosylases flip the target base out of the DNA helix into the enzyme’s active site. Our molecular dynamics simulations of DNA with intact and damaged (oxidized) methyl-cytosine show that the probability of being flipped is similar for damaged and intact methyl-cytosine. However, the accessibility of the different 5-methyl groups allows direct discrimination of the oxidized forms. Hydrogen-bonded patterns that vary between methyl-cytosine forms carrying a carbonyl oxygen atom are likely to be detected by the repair enzymes and may thus help target site recognition. Full article

(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)

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596 KiB

Open AccessArticle

Comparisons of Non-Gaussian Statistical Models in DNA Methylation Analysis

by Zhanyu Ma, Andrew E. Teschendorff, Hong Yu, Jalil Taghia and Jun Guo

Int. J. Mol. Sci. 2014, 15(6), 10835-10854; https://doi.org/10.3390/ijms150610835 - 16 Jun 2014

Cited by 6 | Viewed by 7293

Abstract

As a key regulatory mechanism of gene expression, DNA methylation patterns are widely altered in many complex genetic diseases, including cancer. DNA methylation is naturally quantified by bounded support data; therefore, it is non-Gaussian distributed. In order to capture such properties, we introduce [...] Read more.

As a key regulatory mechanism of gene expression, DNA methylation patterns are widely altered in many complex genetic diseases, including cancer. DNA methylation is naturally quantified by bounded support data; therefore, it is non-Gaussian distributed. In order to capture such properties, we introduce some non-Gaussian statistical models to perform dimension reduction on DNA methylation data. Afterwards, non-Gaussian statistical model-based unsupervised clustering strategies are applied to cluster the data. Comparisons and analysis of different dimension reduction strategies and unsupervised clustering methods are presented. Experimental results show that the non-Gaussian statistical model-based methods are superior to the conventional Gaussian distribution-based method. They are meaningful tools for DNA methylation analysis. Moreover, among several non-Gaussian methods, the one that captures the bounded nature of DNA methylation data reveals the best clustering performance. Full article

(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)

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Review

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1119 KiB

Open AccessReview

DNA and RNA Quadruplex-Binding Proteins

by Václav Brázda, Lucia Hároníková, Jack C. C. Liao and Miroslav Fojta

Int. J. Mol. Sci. 2014, 15(10), 17493-17517; https://doi.org/10.3390/ijms151017493 - 29 Sep 2014

Cited by 199 | Viewed by 16261

Abstract

Four-stranded DNA structures were structurally characterized in vitro by NMR, X-ray and Circular Dichroism spectroscopy in detail. Among the different types of quadruplexes (i-Motifs, minor groove quadruplexes, G-quadruplexes, etc.), the best described are G-quadruplexes which are featured by Hoogsteen base-paring. Sequences with [...] Read more.

Four-stranded DNA structures were structurally characterized in vitro by NMR, X-ray and Circular Dichroism spectroscopy in detail. Among the different types of quadruplexes (i-Motifs, minor groove quadruplexes, G-quadruplexes, etc.), the best described are G-quadruplexes which are featured by Hoogsteen base-paring. Sequences with the potential to form quadruplexes are widely present in genome of all organisms. They are found often in repetitive sequences such as telomeric ones, and also in promoter regions and 5' non-coding sequences. Recently, many proteins with binding affinity to G-quadruplexes have been identified. One of the initially portrayed G-rich regions, the human telomeric sequence (TTAGGG)_n, is recognized by many proteins which can modulate telomerase activity. Sequences with the potential to form G-quadruplexes are often located in promoter regions of various oncogenes. The NHE III₁ region of the c-MYC promoter has been shown to interact with nucleolin protein as well as other G-quadruplex-binding proteins. A number of G-rich sequences are also present in promoter region of estrogen receptor alpha. In addition to DNA quadruplexes, RNA quadruplexes, which are critical in translational regulation, have also been predicted and observed. For example, the RNA quadruplex formation in telomere-repeat-containing RNA is involved in interaction with TRF2 (telomere repeat binding factor 2) and plays key role in telomere regulation. All these fundamental examples suggest the importance of quadruplex structures in cell processes and their understanding may provide better insight into aging and disease development. Full article

(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)

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1072 KiB

Open AccessReview

Chromatin Structure and Dynamics in Hot Environments: Architectural Proteins and DNA Topoisomerases of Thermophilic Archaea

by Valeria Visone, Antonella Vettone, Mario Serpe, Anna Valenti, Giuseppe Perugino, Mosè Rossi and Maria Ciaramella

Int. J. Mol. Sci. 2014, 15(9), 17162-17187; https://doi.org/10.3390/ijms150917162 - 25 Sep 2014

Cited by 14 | Viewed by 8310

Abstract

In all organisms of the three living domains (Bacteria, Archaea, Eucarya) chromosome-associated proteins play a key role in genome functional organization. They not only compact and shape the genome structure, but also regulate its dynamics, which is essential to allow complex genome functions. [...] Read more.

In all organisms of the three living domains (Bacteria, Archaea, Eucarya) chromosome-associated proteins play a key role in genome functional organization. They not only compact and shape the genome structure, but also regulate its dynamics, which is essential to allow complex genome functions. Elucidation of chromatin composition and regulation is a critical issue in biology, because of the intimate connection of chromatin with all the essential information processes (transcription, replication, recombination, and repair). Chromatin proteins include architectural proteins and DNA topoisomerases, which regulate genome structure and remodelling at two hierarchical levels. This review is focussed on architectural proteins and topoisomerases from hyperthermophilic Archaea. In these organisms, which live at high environmental temperature (>80 °C <113 °C), chromatin proteins and modulation of the DNA secondary structure are concerned with the problem of DNA stabilization against heat denaturation while maintaining its metabolic activity. Full article

(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)

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1215 KiB

Open AccessReview

Making the Bend: DNA Tertiary Structure and Protein-DNA Interactions

by Sabrina Harteis and Sabine Schneider

Int. J. Mol. Sci. 2014, 15(7), 12335-12363; https://doi.org/10.3390/ijms150712335 - 14 Jul 2014

Cited by 71 | Viewed by 24758

Abstract

DNA structure functions as an overlapping code to the DNA sequence. Rapid progress in understanding the role of DNA structure in gene regulation, DNA damage recognition and genome stability has been made. The three dimensional structure of both proteins and DNA plays a [...] Read more.

DNA structure functions as an overlapping code to the DNA sequence. Rapid progress in understanding the role of DNA structure in gene regulation, DNA damage recognition and genome stability has been made. The three dimensional structure of both proteins and DNA plays a crucial role for their specific interaction, and proteins can recognise the chemical signature of DNA sequence (“base readout”) as well as the intrinsic DNA structure (“shape recognition”). These recognition mechanisms do not exist in isolation but, depending on the individual interaction partners, are combined to various extents. Driving force for the interaction between protein and DNA remain the unique thermodynamics of each individual DNA-protein pair. In this review we focus on the structures and conformations adopted by DNA, both influenced by and influencing the specific interaction with the corresponding protein binding partner, as well as their underlying thermodynamics. Full article

(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)

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4287 KiB

Open AccessReview

The Self-Assembled Behavior of DNA Bases on the Interface

by Lei Liu, Dan Xia, Lasse H. Klausen and Mingdong Dong

Int. J. Mol. Sci. 2014, 15(2), 1901-1914; https://doi.org/10.3390/ijms15021901 - 27 Jan 2014

Cited by 32 | Viewed by 9245

Abstract

A successful example of self-assembly in a biological system is that DNA can be an excellent agent to self-assemble into desirable two and three-dimensional nanostructures in a well-ordered manner by specific hydrogen bonding interactions between the DNA bases. The self-assembly of DNA bases [...] Read more.

A successful example of self-assembly in a biological system is that DNA can be an excellent agent to self-assemble into desirable two and three-dimensional nanostructures in a well-ordered manner by specific hydrogen bonding interactions between the DNA bases. The self-assembly of DNA bases have played a significant role in constructing the hierarchical nanostructures. In this review article we will introduce the study of nucleic acid base self-assembly by scanning tunneling microscopy (STM) at vacuum and ambient condition (the liquid/solid interface), respectively. From the ideal condition to a more realistic environment, the self-assembled behaviors of DNA bases are introduced. In a vacuum system, the energetic advantages will dominate the assembly formation of DNA bases, while at ambient condition, more factors such as conformational freedom and the biochemical environment will be considered. Therefore, the assemblies of DNA bases at ambient condition are different from the ones obtained under vacuum. We present the ordered nanostructures formed by DNA bases at both vacuum and ambient condition. To construct and tailor the nanostructure through the interaction between DNA bases, it is important to understand the assembly behavior and features of DNA bases and their derivatives at ambient condition. The utilization of STM offers the advantage of investigating DNA base self-assembly with sub-molecular level resolution at the surface. Full article

(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)

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