scholarly journals A world beyond double-helical nucleic acids: the structural diversity of tetra-stranded G-quadruplexes

ChemTexts ◽  
2021 ◽  
Vol 7 (4) ◽  
Author(s):  
Klaus Weisz
Keyword(s):  
Hydrogen Bond ◽  
Nucleic Acids ◽  
Genetic Information ◽  
Structural Diversity ◽  
Base Pairing ◽  
Rna Sequences ◽  
Dna And Rna ◽  
Regulatory Functions ◽  
Insight Into

AbstractNucleic acids can adopt various secondary structures including double-, triple-, and tetra-stranded helices that differ by the specific hydrogen bond mediated pairing pattern between their nucleobase constituents. Whereas double-helical DNA relies on Watson–Crick base pairing to play a prominent role in storing genetic information, G-quadruplexes are tetra-stranded structures that are formed by the association of guanine bases from G-rich DNA and RNA sequences. During the last few decades, G-quadruplexes have attracted considerable interest after the realization that they form and exert regulatory functions in vivo. In addition, quadruplex architectures have also been recognized as versatile and powerful tools in a growing number of technological applications. To appreciate the astonishing structural diversity of these tetra-stranded structures and to give some insight into basic interactions that govern their folding, this article gives an overview of quadruplex structures and rules associated with the formation of different topologies. A brief discussion will also focus on nonconventional quadruplexes as well as on general principles when targeting quadruplexes with ligands. Graphic abstract

Methylation of Guanine in vivo by the Organophosphorus Insecticide Methamidophos*

1987 ◽  
Vol 42 (1-2) ◽  
pp. 17-20 ◽  
Author(s):  
Salah M . A . D . Zayed ◽  
Fathya M. Mahdi
Keyword(s):  
Nucleic Acids ◽  
Mouse Liver ◽  
Organophosphorus Insecticide ◽  
Appreciable Amount ◽  
Dna And Rna ◽  
Applied Dose

Abstract The methylating capability of methamidophos, assayed by the formation of [7-14C]methylguanine in mouse liver, was investigated using a 14C-insecticide labelled at the O -CH3 group. Following i.p. administration of the toxicant, [7-14C]methylguanine could be isolated from liver nucleic acids of treated mice. The amount of 14C-label reached its maximum 6 h follow ing administration of the insecticide. At maximum 14C-labelling, the amount of 7-methylguanine calculated as fraction of applied dose, was 20-22 × 10-4 and 98 -104 x-4, for DNA and RNA , respectively. The results obtained indicate also, that an appreciable amount of I4C-activity is incorporated via the C-1 pool.

scholarly journals De Novo Nucleic Acids: A Review of Synthetic Alternatives to DNA and RNA That Could Act as Bio-Information Storage Molecules

Life ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 346
Author(s):  
Kevin G Devine ◽  
Sohan Jheeta
Keyword(s):  
Nucleic Acids ◽  
Genetic Information ◽  
De Novo ◽  
Chemical Properties ◽  
Amino Acid Sequences ◽  
Information Storage ◽  
Heterocyclic Base ◽  
Dna And Rna ◽  
Phosphate Backbone ◽  
Physical And Chemical

Modern terran life uses several essential biopolymers like nucleic acids, proteins and polysaccharides. The nucleic acids, DNA and RNA are arguably life’s most important, acting as the stores and translators of genetic information contained in their base sequences, which ultimately manifest themselves in the amino acid sequences of proteins. But just what is it about their structures; an aromatic heterocyclic base appended to a (five-atom ring) sugar-phosphate backbone that enables them to carry out these functions with such high fidelity? In the past three decades, leading chemists have created in their laboratories synthetic analogues of nucleic acids which differ from their natural counterparts in three key areas as follows: (a) replacement of the phosphate moiety with an uncharged analogue, (b) replacement of the pentose sugars ribose and deoxyribose with alternative acyclic, pentose and hexose derivatives and, finally, (c) replacement of the two heterocyclic base pairs adenine/thymine and guanine/cytosine with non-standard analogues that obey the Watson–Crick pairing rules. This manuscript will examine in detail the physical and chemical properties of these synthetic nucleic acid analogues, in particular on their abilities to serve as conveyors of genetic information. If life exists elsewhere in the universe, will it also use DNA and RNA?

scholarly journals Synthetic Life with Alternative Nucleic Acids as Genetic Materials

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3483
Author(s):  
Peng Nie ◽  
Yanfen Bai ◽  
Hui Mei
Keyword(s):  
Nucleic Acids ◽  
Genetic Information ◽  
Structural Parameters ◽  
Living Cells ◽  
Information Storage ◽  
Chemically Modified ◽  
Synthetic Life ◽  
Living Organisms

DNA, the fundamental genetic polymer of all living organisms on Earth, can be chemically modified to embrace novel functions that do not exist in nature. The key chemical and structural parameters for genetic information storage, heredity, and evolution have been elucidated, and many xenobiotic nucleic acids (XNAs) with non-canonical structures are developed as alternative genetic materials in vitro. However, it is still particularly challenging to replace DNAs with XNAs in living cells. This review outlines some recent studies in which the storage and propagation of genetic information are achieved in vivo by expanding genetic systems with XNAs.

THE SYNTHESIS OF DNA AND RNA IN NORMAL HUMAN ENDOMETRIUM IN SHORT-TERM INCUBATION IN VITRO AND ITS RESPONSE TO OESTRADIOL AND PROGESTERONE

1970 ◽  
Vol 48 (1) ◽  
pp. 17-28 ◽  
Author(s):  
S. NORDQVIST
Keyword(s):  
Nucleic Acids ◽  
Dna Synthesis ◽  
Acid Synthesis ◽  
Short Term ◽  
Normal Endometrium ◽  
Dna And Rna ◽  
Progesterone Synthesis ◽  
Normal Human

SUMMARY A method is described for short-term incubations in vitro of normal endometrium for the study of nucleic acid synthesis. Tissue suspensions of specimens obtained at curettage were incubated with and without hormones in a medium consisting of Parker's 199 medium and 20% adult human serum; [3H]thymidine and [14C]uridine were added. The isotope uptake into the nucleic acids was determined and related to the total amount of DNA in each sample. Marked variation in DNA synthesis was noted in endometria obtained at different phases of the menstrual cycle. RNA synthesis varied less. After the addition of progesterone, synthesis of both nucleic acids was reduced. The magnitude of this response varied in different endometria. Thus DNA synthesis in endometria already under strong progesterone influence in vivo (midsecretory phase) was least affected when progesterone was added in vitro.

scholarly journals RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA

2013 ◽  
Vol 210 (11) ◽  
pp. 2447-2463 ◽  
Author(s):  
Cherilyn M. Sirois ◽  
Tengchuan Jin ◽  
Allison L. Miller ◽  
Damien Bertheloot ◽  
Hirotaka Nakamura ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Inflammatory Responses ◽  
Immune Recognition ◽  
Dna Uptake ◽  
Rna Molecules ◽  
Receptor Complexes ◽  
Dna And Rna ◽  
Signaling Receptors ◽  
Mammalian Immune System

Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection and tissue damage. Activation of immune signaling receptors by nucleic acids is controlled by limiting the access of DNA and RNA to intracellular receptors, but the mechanisms by which endosome-resident receptors encounter nucleic acids from the extracellular space are largely undefined. In this study, we show that the receptor for advanced glycation end-products (RAGE) promoted DNA uptake into endosomes and lowered the immune recognition threshold for the activation of Toll-like receptor 9, the principal DNA-recognizing transmembrane signaling receptor. Structural analysis of RAGE–DNA complexes indicated that DNA interacted with dimers of the outermost RAGE extracellular domains, and could induce formation of higher-order receptor complexes. Furthermore, mice deficient in RAGE were unable to mount a typical inflammatory response to DNA in the lung, indicating that RAGE is important for the detection of nucleic acids in vivo.

scholarly journals CRISPR/Cas: Advances, Limitations, and Applications for Precision Cancer Research

2021 ◽  
Vol 8 ◽  
Author(s):  
Yue Yang ◽  
Jin Xu ◽  
Shuyu Ge ◽  
Liqin Lai
Keyword(s):  
Cancer Research ◽  
Targeted Delivery ◽  
Genome Engineering ◽  
Resistance Mechanisms ◽  
Rna Sequences ◽  
Dna And Rna ◽  
Recent Developments ◽  
Associated Proteins ◽  
Cancer Tumor

Cancer is one of the most leading causes of mortalities worldwide. It is caused by the accumulation of genetic and epigenetic alterations in 2 types of genes: tumor suppressor genes (TSGs) and proto-oncogenes. In recent years, development of the clustered regularly interspaced short palindromic repeats (CRISPR) technology has revolutionized genome engineering for different cancer research ranging for research ranging from fundamental science to translational medicine and precise cancer treatment. The CRISPR/CRISPR associated proteins (CRISPR/Cas) are prokaryote-derived genome editing systems that have enabled researchers to detect, image, manipulate and annotate specific DNA and RNA sequences in various types of living cells. The CRISPR/Cas systems have significant contributions to discovery of proto-oncogenes and TSGs, tumor cell epigenome normalization, targeted delivery, identification of drug resistance mechanisms, development of high-throughput genetic screening, tumor models establishment, and cancer immunotherapy and gene therapy in clinics. Robust technical improvements in CRISPR/Cas systems have shown a considerable degree of efficacy, specificity, and flexibility to target the specific locus in the genome for the desired applications. Recent developments in CRISPRs technology offers a significant hope of medical cure against cancer and other deadly diseases. Despite significant improvements in this field, several technical challenges need to be addressed, such as off-target activity, insufficient indel or low homology-directed repair (HDR) efficiency, in vivo delivery of the Cas system components, and immune responses. This study aims to overview the recent technological advancements, preclinical and perspectives on clinical applications of CRISPR along with their advantages and limitations. Moreover, the potential applications of CRISPR/Cas in precise cancer tumor research, genetic, and other precise cancer treatments discussed.

scholarly journals A Novel G-Quadruplex Binding Protein in Yeast—Slx9

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1774 ◽  
Author(s):  
Silvia Götz ◽  
Satyaprakash Pandey ◽  
Sabrina Bartsch ◽  
Stefan Juranek ◽  
Katrin Paeschke
Keyword(s):  
Binding Protein ◽  
Sequence Motifs ◽  
Dna And Rna ◽  
G4 Dna ◽  
G Quadruplex ◽  
High Thermodynamic Stability ◽  
Guanine Base ◽  
Regulatory Functions

G-quadruplex (G4) structures are highly stable four-stranded DNA and RNA secondary structures held together by non-canonical guanine base pairs. G4 sequence motifs are enriched at specific sites in eukaryotic genomes, suggesting regulatory functions of G4 structures during different biological processes. Considering the high thermodynamic stability of G4 structures, various proteins are necessary for G4 structure formation and unwinding. In a yeast one-hybrid screen, we identified Slx9 as a novel G4-binding protein. We confirmed that Slx9 binds to G4 DNA structures in vitro. Despite these findings, Slx9 binds only insignificantly to G-rich/G4 regions in Saccharomyces cerevisiae as demonstrated by genome-wide ChIP-seq analysis. However, Slx9 binding to G4s is significantly increased in the absence of Sgs1, a RecQ helicase that regulates G4 structures. Different genetic and molecular analyses allowed us to propose a model in which Slx9 recognizes and protects stabilized G4 structures in vivo.

scholarly journals Seven-base-pair inverted repeats in DNA form stable hairpins in vivo in Saccharomyces cerevisiae.

Genetics ◽  
1991 ◽  
Vol 129 (3) ◽  
pp. 669-673 ◽  
Author(s):  
D K Nag ◽  
T D Petes
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Base Pair ◽  
Inverted Repeat ◽  
Inverted Repeats ◽  
Base Pairing ◽  
Yeast Saccharomyces Cerevisiae ◽  
Genetic Method ◽  
Dna And Rna ◽  
Palindromic Sequences

Abstract Palindromic sequences in single-stranded DNA and RNA have the potential for intrastrand base pairing, resulting in formation of "hairpin" structures. We previously reported a genetic method for detecting such structures in vivo in the yeast Saccharomyces cerevisiae. Below, we describe evidence indicating that a 14-base-pair palindrome (7 bp per inverted repeat) is sufficient for formation of a hairpin in vivo.

scholarly journals Daniel McGillivray Brown. 3 February 1923—24 April 2012

2018 ◽  
Vol 66 ◽  
pp. 79-100
Author(s):  
Michael J. Gait
Keyword(s):  
Nucleic Acids ◽  
Chemical Structure ◽  
Antiviral Agent ◽  
Chemical Methods ◽  
Rna Sequences ◽  
Chemical Structures ◽  
Phosphodiester Linkage ◽  
Dna And Rna ◽  
University Of Cambridge ◽  
Error Catastrophe

Dan Brown was a nucleic acids chemist of the highest order, beginning with pioneering work under Lord Alexander Todd in the 1950s at University of Cambridge on chemical methods for synthesis of nucleosides and nucleotides. This work helped to confirm the furanose chemical structure of the sugar in nucleosides as well as the 3′-5′ phosphodiester linkage in DNA and RNA, perhaps the most well thought of achievement of his career. Later, as a chemistry department lecturer, he established the chemical structures of glycerol monophosphoinositides as well as triphosphoinositides. Turning back to the nucleic acids in 1961, he became fascinated by the effect of mutagens on DNA. He elucidated the mechanism for the reaction of hydroxylamine on cytidine to form an initial ‘bis-adduct’ and thereafter N 6 -hydroxycytidine. Moving in 1982 to the MRC Laboratory of Molecular Biology, he developed a method to prepare single-stranded DNA probes for detection of RNA sequences and in addition worked on a novel automated device for oligonucleotide synthesis. Reverting to his interest in mutagens, he then designed and synthesized hydrogen bonding degenerate bases and developed novel P and K modified pyrimidine and purine bases respectively as transition mutagens. Finally, he synthesized the base analogue 5-nitroindole as a potential universal base, which became useful in cycle DNA sequencing, and in addition developed the concept of ‘error catastrophe’ for the ribonucleoside of the P base as an antiviral agent. The P, K and 5-nitroindole bases became the most valued chemical entities of his career to molecular biologists. His legacy to the nucleic acids includes both his significant contributions to studies of the chemical nature of DNA and RNA and their constituents as well as a variety of enabling nucleic acids chemistry methods and mechanisms of DNA mutagenicity.

scholarly journals Machines on Genes: Enzymes that Make, Break and Move DNA and RNA

2010 ◽  
Vol 38 (2) ◽  
pp. 381-383 ◽  
Author(s):  
W. Marshall Stark ◽  
Ben F. Luisi ◽  
Richard P. Bowater
Keyword(s):  
Gene Expression ◽  
Molecular Biology ◽  
Nucleic Acids ◽  
Present Article ◽  
Genetic Information ◽  
Clear View ◽  
Dna And Rna ◽  
Repair Enzymes ◽  
University Of Cambridge ◽  
Enzyme Substrates

As the vital information repositories of the cell, the nucleic acids DNA and RNA pose many challenges as enzyme substrates. To produce, maintain and repair DNA and RNA, and to extract the genetic information that they encode, a battery of remarkable enzymes has evolved, which includes translocases, polymerases/replicases, helicases, nucleases, topoisomerases, transposases, recombinases, repair enzymes and ribosomes. An understanding of how these enzymes function is essential if we are to have a clear view of the molecular biology of the cell and aspire to manipulate genomes and gene expression to our advantage. To bring together scientists working in this fast-developing field, the Biochemical Society held a Focused Meeting, ‘Machines on Genes: Enzymes that Make, Break and Move DNA and RNA’, at Robinson College, University of Cambridge, U.K., in August 2009. The present article summarizes the research presented at this meeting and the reviews associated with the talks which are published in this issue of Biochemical Society Transactions.

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