scholarly journals DNA sequence encodes the position of DNA supercoils

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sung Hyun Kim ◽  
Mahipal Ganji ◽  
Eugene Kim ◽  
Jaco van der Torre ◽  
Elio Abbondanzieri ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Structural Information ◽  
Three Dimensional ◽  
Decisive Role ◽  
Chromosomal Dna ◽  
Dna Structures ◽  
Cellular Processes ◽  
Specific Sequences ◽  
Good Agreement

The three-dimensional organization of DNA is increasingly understood to play a decisive role in vital cellular processes. Many studies focus on the role of DNA-packaging proteins, crowding, and confinement in arranging chromatin, but structural information might also be directly encoded in bare DNA itself. Here, we visualize plectonemes (extended intertwined DNA structures formed upon supercoiling) on individual DNA molecules. Remarkably, our experiments show that the DNA sequence directly encodes the structure of supercoiled DNA by pinning plectonemes at specific sequences. We develop a physical model that predicts that sequence-dependent intrinsic curvature is the key determinant of pinning strength and demonstrate this simple model provides very good agreement with the data. Analysis of several prokaryotic genomes indicates that plectonemes localize directly upstream of promoters, which we experimentally confirm for selected promotor sequences. Our findings reveal a hidden code in the genome that helps to spatially organize the chromosomal DNA.

scholarly journals DNA sequence encodes the position of DNA supercoils

2017 ◽  
Author(s):  
Sung Hyun Kim ◽  
Mahipal Ganji ◽  
Jaco van der Torre ◽  
Elio Abbondanzieri ◽  
Cees Dekker
Keyword(s):  
Dna Sequence ◽  
Single Molecule ◽  
Dna Sequences ◽  
Structural Information ◽  
Three Dimensional ◽  
Decisive Role ◽  
Dimensional Structure ◽  
Transcription Start Sites ◽  
Cellular Processes

AbstractThe three-dimensional structure of DNA is increasingly understood to play a decisive role in gene regulation and other vital cellular processes, which has triggered an explosive growth of research on the spatial architecture of the genome. Many studies focus on the role of various DNA-packaging proteins, crowding, and confinement in organizing chromatin, but structural information might also be directly encoded in bare DNA itself. Here, we use a fluorescence-based single-molecule technique to visualize plectonemes, the extended intertwined DNA loops that form upon twisting DNA. Remarkably, we find that the underlying DNA sequence directly encodes the structure of supercoiled DNA by pinning plectonemes at specific positions. We explore a variety of DNA sequences to determine what features influence pinning, and we develop a physical model that predicts the level of plectoneme pinning in excellent agreement with the data. The intrinsic curvature measured over a range of ~70 base pairs is found to be the key property governing the supercoiled structure of DNA. Our model predicts that plectonemes are likely to localize directly upstream of prokaryotic transcription start sites, and this prediction is experimentally verifiedin vitro.Our results reveal a hidden code in DNA that helps to spatially organize the genome.

Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim
Keyword(s):  
Breast Cancer ◽  
Hox Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Genome Structure ◽  
Control Cell ◽  
Three Dimensional ◽  
Cellular Processes ◽  
Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

scholarly journals The Presence and Localization of G-Quadruplex Forming Sequences in the Domain of Bacteria

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1711 ◽  
Author(s):  
Martin Bartas ◽  
Michaela Čutová ◽  
Václav Brázda ◽  
Patrik Kaura ◽  
Jiří Šťastný ◽  
...  
Keyword(s):  
Regulatory Sequences ◽  
Bacterial Genomes ◽  
Dna Structures ◽  
Cellular Processes ◽  
G Quadruplex ◽  
Data Point ◽  
Functional Relevance

The role of local DNA structures in the regulation of basic cellular processes is an emerging field of research. Amongst local non-B DNA structures, the significance of G-quadruplexes was demonstrated in the last decade, and their presence and functional relevance has been demonstrated in many genomes, including humans. In this study, we analyzed the presence and locations of G-quadruplex-forming sequences by G4Hunter in all complete bacterial genomes available in the NCBI database. G-quadruplex-forming sequences were identified in all species, however the frequency differed significantly across evolutionary groups. The highest frequency of G-quadruplex forming sequences was detected in the subgroup Deinococcus-Thermus, and the lowest frequency in Thermotogae. G-quadruplex forming sequences are non-randomly distributed and are favored in various evolutionary groups. G-quadruplex-forming sequences are enriched in ncRNA segments followed by mRNAs. Analyses of surrounding sequences showed G-quadruplex-forming sequences around tRNA and regulatory sequences. These data point to the unique and non-random localization of G-quadruplex-forming sequences in bacterial genomes.

scholarly journals Overview of RNA G-quadruplex structures

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Magdalena Małgowska
Keyword(s):  
Three Dimensional ◽  
Telomere Maintenance ◽  
Structural Studies ◽  
Biological Functions ◽  
Cellular Processes ◽  
Novel Drugs ◽  
G Quadruplex ◽  
Conformational Diversity

G-quadruplexes are non-canonical secondary structures which may be formed by guanine rich sequences, both in vitro and in living cells. The number of biological functions assigned to these structural motifs has grown rapidly since the discovery of their involvement in the telomere maintenance. Knowledge of the three-dimensional structures of G-quadruplexes plays an important role in understanding their conformational diversity, physiological functions, and in the design of novel drugs targeting G-quadruplexes. For the last decades, structural studies have been mainly focused on the DNA G-quadruplexes. Their RNA counterparts gained an increased interest along with still-emerging recognition of the central role of RNA in multiple cellular processes. In this review we focus on structural properties of RNA G-quadruplexes, based on high-resolution structures, available in RCSB PDB data base and on structural models. In addition, we point out to the current challenges in this field of research.

scholarly journals The STRIPAK component SipC is involved in morphology and cell-fate determination in the nematode-trapping fungus Duddingtonia flagrans

Genetics ◽  
2021 ◽  
Author(s):  
Valentin Wernet ◽  
Jan Wäckerle ◽  
Reinhard Fischer
Keyword(s):  
Cell Fate ◽  
Three Dimensional ◽  
Loop Formation ◽  
Duddingtonia Flagrans ◽  
Multicellular Development ◽  
Hyphal Fusion ◽  
Cellular Processes ◽  
Complex Functions ◽  
Cytochalasin A

Abstract The striatin-interacting phosphatase and kinase complex (STRIPAK) is a highly conserved eukaryotic signaling hub involved in the regulation of many cellular processes. In filamentous fungi, STRIPAK controls multicellular development, hyphal fusion, septation and pathogenicity. In this study we analyzed the role of the STRIPAK complex in the nematode-trapping fungus Duddingtonia flagrans which forms three-dimensional, adhesive trapping networks to capture Caenorhabditis elegans. Trap networks consist of several hyphal loops which are morphologically and functionally different from vegetative hyphae. We show that lack of the STRIPAK component SipC (STRIP1/2/HAM-2/PRO22) results in incomplete loop formation and column-like trap structures with elongated compartments. The misshapen or incomplete traps lost their trap identity and continued growth as vegetative hyphae. The same effect was observed in the presence of the actin cytoskeleton drug cytochalasin A. These results could suggest a link between actin and STRIPAK complex functions.

scholarly journals Non-B DNA: a major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome

2021 ◽  
Vol 49 (3) ◽  
pp. 1497-1516
Author(s):  
Wilfried M Guiblet ◽  
Marzia A Cremona ◽  
Robert S Harris ◽  
Di Chen ◽  
Kristin A Eckert ◽  
...  
Keyword(s):  
Large Scale ◽  
Nucleotide Substitution ◽  
Genetic Diseases ◽  
Nucleotide Polymorphisms ◽  
Dna Structures ◽  
Cellular Processes ◽  
Genome Wide ◽  
Dna Types ◽  
Flanking Regions

Abstract Approximately 13% of the human genome can fold into non-canonical (non-B) DNA structures (e.g. G-quadruplexes, Z-DNA, etc.), which have been implicated in vital cellular processes. Non-B DNA also hinders replication, increasing errors and facilitating mutagenesis, yet its contribution to genome-wide variation in mutation rates remains unexplored. Here, we conducted a comprehensive analysis of nucleotide substitution frequencies at non-B DNA loci within noncoding, non-repetitive genome regions, their ±2 kb flanking regions, and 1-Megabase windows, using human-orangutan divergence and human single-nucleotide polymorphisms. Functional data analysis at single-base resolution demonstrated that substitution frequencies are usually elevated at non-B DNA, with patterns specific to each non-B DNA type. Mirror, direct and inverted repeats have higher substitution frequencies in spacers than in repeat arms, whereas G-quadruplexes, particularly stable ones, have higher substitution frequencies in loops than in stems. Several non-B DNA types also affect substitution frequencies in their flanking regions. Finally, non-B DNA explains more variation than any other predictor in multiple regression models for diversity or divergence at 1-Megabase scale. Thus, non-B DNA substantially contributes to variation in substitution frequencies at small and large scales. Our results highlight the role of non-B DNA in germline mutagenesis with implications to evolution and genetic diseases.

scholarly journals Notch Signaling and MicroRNA: The Dynamic Duo Steering Between Neurogenesis and Glioblastomas

2021 ◽  
Vol 67 (2) ◽  
pp. 33-43
Author(s):  
Zeeshan Javed ◽  
Khushbukhat Khan ◽  
Qamar Raza ◽  
Haleema Sadia ◽  
Faiez Ahmad Shah ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Small Molecules ◽  
Neuronal Cell ◽  
Decisive Role ◽  
Eukaryotic Cells ◽  
Diagnostic Tools ◽  
Special Focus ◽  
Cellular Processes ◽  
Development And Differentiation

Notch signaling is an evolutionary conserved pathway that plays a central role in development and differentiation of eukaryotic cells. It has been well documented that Notch signaling is inevitable for neuronal cell growth and homeostasis. It regulates process of differentiation from early embryonic stages to fully developed brain. To achieve this streamlined development of neuronal cells, a number of cellular processes are being orchestrated by the Notch signaling. Abrogated Notch signaling is related to several brain tumors, including glioblastomas. On the other hand, microRNAs are small molecules that play decisive role in mediating and modulating Notch signaling. This review discusses the crucial role of Notch signaling in development of nervous system and how this versatile pathway interplay with microRNAs in glioblastoma. This review sheds light on interplay between abrogated Notch signaling and miRNAs in the regulation of neuronal differentiation with special focus on miRNAs mediated regulation of tumorigenesis in glioblastoma. Furthermore, it discusses different aspects of neurogenesis modulated by the Notch signaling that could be exploited for the identification of new diagnostic tools and therapies for the treatment of glioblastoma.

scholarly journals Volumetric Properties of Four-Stranded DNA Structures

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 813
Author(s):  
Tigran V. Chalikian ◽  
Robert B. Macgregor
Keyword(s):  
Regulation Of Transcription ◽  
Solvent Interactions ◽  
Dna Structures ◽  
Cellular Processes ◽  
Molecular Determinants ◽  
Telomere Biology ◽  
The Stability

Four-stranded non-canonical DNA structures including G-quadruplexes and i-motifs have been found in the genome and are thought to be involved in regulation of biological function. These structures have been implicated in telomere biology, genomic instability, and regulation of transcription and translation events. To gain an understanding of the molecular determinants underlying the biological role of four-stranded DNA structures, their biophysical properties have been extensively studied. The limited libraries on volume, expansibility, and compressibility accumulated to date have begun to provide insights into the molecular origins of helix-to-coil and helix-to-helix conformational transitions involving four-stranded DNA structures. In this article, we review the recent progress in volumetric investigations of G-quadruplexes and i-motifs, emphasizing how such data can be used to characterize intra-and intermolecular interactions, including solvation. We describe how volumetric data can be interpreted at the molecular level to yield a better understanding of the role that solute–solvent interactions play in modulating the stability and recognition events of nucleic acids. Taken together, volumetric studies facilitate unveiling the molecular determinants of biological events involving biopolymers, including G-quadruplexes and i-motifs, by providing one more piece to the thermodynamic puzzle describing the energetics of cellular processes in vitro and, by extension, in vivo.

scholarly journals A STUDY OF THE ROLE OF MICRORNA IN PITUITARY ADENOMA

2018 ◽  
Vol 5 (2) ◽  
pp. 8-15
Author(s):  
I. F. Gareev ◽  
O. A. Beylerli
Keyword(s):  
Pituitary Adenoma ◽  
Target Genes ◽  
Decisive Role ◽  
Cellular Processes ◽  
New Class ◽  
Number Of Genes ◽  
Non Coding Rnas ◽  
New Biomarkers ◽  
New Evidence

MicroRNAs are a new class of small non-coding RNAs, a length of 18–22 nucleotides that play a decisive role as posttranscriptional regulators of gene expression. Due to the large number of genes, regulated microRNAs, microRNAs are involved in many cellular processes. The study of the impairment of the expression of the target genes of microRNA, often associated with changes in important biological characteristics, provides a significant understanding of the role of microRNAs in oncogenesis. New evidence suggests that aberrant microRNA expression or dysregulation of endogenous microRNAs affects the onset and development of tumors, including adenomas of the pituitary gland. In this review, the significance of some microRNAs in the pathology of the pituitary adenoma will be assessed, as well as data on the study of microRNAs as therapeutic targets and new biomarkers.

scholarly journals Experimental study of the three-dimensional flow structure in matrix channels

2021 ◽  
Vol 2057 (1) ◽  
pp. 012027
Author(s):  
M V Philippov ◽  
I A Chokhar ◽  
A V Zolotukhin ◽  
A V Barsukov ◽  
V V Terekhov ◽  
...  
Keyword(s):  
Experimental Study ◽  
Three Dimensional ◽  
Decisive Role ◽  
Three Dimensional Flow ◽  
Matrix Channel ◽  
Dimensional Flow ◽  
The Matrix ◽  
Role Based ◽  
High Degree

Abstract The article presents an experimental study of the turbulent flow in matrix channels. Using the modern optical contactless laser Doppler anemometer (LDA) method, an idea of the turbulent three-dimensional flow inside the cells of matrix channels is developed. The results of the study of the matrix channel show that the so-called vortex matrix effect is not formed. The most important factor that causes a high degree of heat transfer from the walls is the intense spiral motion between the matrix cells. The measurements also show that the effects associated with the lateral boundaries of the channel play a significant role. Based on the assumption of the decisive role of the spiral flow between the cells of the matrix channel, a formula for the integral pressure loss is proposed.

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