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.

scholarly journals Circulating nucleic acids in blood as biomarkers

2009 ◽  
Vol 16 (1) ◽  
Author(s):  
Reidun Øvstebø ◽  
Peter Kierulf ◽  
Kari Bente Foss Haug
Keyword(s):  
Gene Expression ◽  
Nucleic Acids ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Global Gene Expression ◽  
Short Review ◽  
Drug Susceptibility ◽  
Nucleotide Polymorphisms ◽  
Cytochrom P450 ◽  
Dna And Rna

<p>This short review on a rapidly expanding domain in biomarkers focuses on the value of markers derived from either circulating intracellular DNA and RNA (leukocytes) or from free DNA and RNA in plasma or serum. In circulating intracellular DNA biomarkers, importance has been pointed to reside in the ever increasing number of SNPs directly related to disease such as hemochromatosis or associated with genetic make up that leads to different drug-susceptibility. Quantitative gene expression profiling, increasingly using global expression platforms, is gaining momentum in various disease states such as cancer, inflammation, cardiovascular disease and diabetes. Circulating free nucleic acids in plasma or serum gain in importance as biomarkers particularly in cancer and foeto-maternal understanding. The surprising recent findings of circulating free mRNA carries the potential of examining normal and diseased plasma for global gene expression profiling – opening avenues to new biomarkers. When appropriate, this review gives reference to methodological considerations and refers the readers to important literature in the fields</p><p>I denne korte oversiktsartikkelen redegjøres det for et biomarkørfelt som utvikler seg hurtig. Gjennom en blodprøve kan man få kjennskap til forandringer i sirkulerende leucocytter, intracellulære nukleinsyrer (DNA og RNA) og fritt DNA og RNA fra plasma eller serum. Single Nucleotide Polymorphisms (SNPs) i DNA har allerede bekreftet sine muligheter som biomarkører (f.eks. Hemokromatose, Faktor V Leiden, Cytochrom P450 (CYP’er)). Stadig flere SNP’er vinner innpass i klinisk sammenheng. Siden sirkulerende hvite blodlegemer kan sies kontinuerlig å overvåke kroppens organer og vev, og dette avspeiles i disse blodcellers genekspresjon (RNA), knyttes det i dag forventninger til sykdomsspesifikke genekspresjonsprofiler. Både ved visse kreftformer, betennelsestilstander og hjertekar-sykdom viser hvite blodlegemer mer eller mindre tydelig sykdomsspesifikke genekspresjonsprofiler. Denne type sykdomsspesifikke genekspresjonsmarkører vil bli økende viktig fremover. Ved slike markører vil man kunne ha nytte av kvantitativ måling av enkeltmarkører, og også globale genekspresjonsprofiler på mikroarray-plattformer. Sirkulerende fritt DNA og kanskje særlig RNA i plasma åpner for nye sykdomsmarkører i første rekke ved forskjellige kreftformer og ved foeto-maternelle problemstillinger. Oversikten gir også en henvisning til metodologiske referanser i disse feltene.</p>

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 Understanding RNA modifications: the promises and technological bottlenecks of the ‘epitranscriptome’

Open Biology ◽  
2017 ◽  
Vol 7 (5) ◽  
pp. 170077 ◽  
Author(s):  
Matthias Schaefer ◽  
Utkarsh Kapoor ◽  
Michael F. Jantsch
Keyword(s):  
Gene Expression ◽  
Mass Spectrometry ◽  
Molecular Biology ◽  
Genetic Information ◽  
Biological Function ◽  
Rna Modifications ◽  
Single Nucleotide ◽  
Technological Advances ◽  
Nucleotide Resolution ◽  
Single Nucleotide Resolution

The discovery of mechanisms that alter genetic information via RNA editing or introducing covalent RNA modifications points towards a complexity in gene expression that challenges long-standing concepts. Understanding the biology of RNA modifications represents one of the next frontiers in molecular biology. To this date, over 130 different RNA modifications have been identified, and improved mass spectrometry approaches are still adding to this list. However, only recently has it been possible to map selected RNA modifications at single-nucleotide resolution, which has created a number of exciting hypotheses about the biological function of RNA modifications, culminating in the proposition of the ‘epitranscriptome’. Here, we review some of the technological advances in this rapidly developing field, identify the conceptual challenges and discuss approaches that are needed to rigorously test the biological function of specific RNA modifications.

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

scholarly journals Auto-qPCR: A Python based web app for automated and reproducible analysis of qPCR data

2021 ◽  
Author(s):  
Gilles Maussion ◽  
Rhalena A. Thomas ◽  
Iveta Demirova ◽  
Gracia Gu ◽  
Eddie Cai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Biology ◽  
Data Processing ◽  
Reference Sample ◽  
Basic Research ◽  
Relative Quantification ◽  
Qpcr Data ◽  
Dna And Rna ◽  
Duplication Events ◽  
Programming Knowledge

AbstractQuantifying changes in DNA and RNA levels is an essential component of any molecular biology toolkit. Quantitative real time PCR (qPCR) techniques, in both clinical and basic research labs, have evolved to become both routine and standardized. However, the analysis of qPCR data includes many steps that are time consuming and cumbersome, which can lead to mistakes and misinterpretation of data. To address this bottleneck, we have developed an open source software, written in Python, to automate the processing of csv output files from any qPCR machine, using standard calculations that are usually performed manually. Auto-qPCR is a tool that saves time when computing this type of data, helping to ensure standardization of qPCR experiment analyses. Unlike other software packages that process qPCR data, our web-based app (http://auto-q-pcr.com/) is easy to use and does not require programming knowledge or software installation. Additionally, we provide examples of four different data processing modes within one program: (1) cDNA quantification to identify genomic deletion or duplication events, (2) assessment of gene expression levels using an absolute model, (3) relative quantification, and (4) relative quantification with a reference sample. Auto-qPCR also includes options for statistical analysis of the data. Using this software, we performed analysis of differential gene expression following an initial data processing and provide graphs of the findings prepared through the Auto-qPCR program. Thus, our open access Auto-qPCR software saves the time of manual data analysis and provides a more systematic workflow, minimizing the risk of errors when done manually. Our program constitutes a new tool that can be incorporated into bioinformatic and molecular biology pipelines in clinical and research labs.

scholarly journals Reimagining the Power of Nucleic Acids as Therapeutic and Diagnostic Agents

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1707
Author(s):  
Anthony Berdis
Keyword(s):  
Molecular Biology ◽  
Nucleic Acids ◽  
Genetic Information ◽  
Central Dogma ◽  
Diagnostic Agents ◽  
Typical Cell

The central dogma of molecular biology proposes that in a typical cell, the flow of genetic information proceeds from DNA to RNA to polypeptide [...]

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 DNA and RNA topoisomerase activities of Top3β are promoted by mediator protein Tudor domain-containing protein 3

2016 ◽  
Vol 113 (38) ◽  
pp. E5544-E5551 ◽  
Author(s):  
Grace Ee-Lu Siaw ◽  
I-Fen Liu ◽  
Po-Yen Lin ◽  
Michael D. Been ◽  
Tao-shih Hsieh
Keyword(s):  
Gene Expression ◽  
Nucleic Acids ◽  
Specific Binding ◽  
Dna And Rna ◽  
Biochemical Assays ◽  
Binding Preference ◽  
Mediator Protein ◽  
Tudor Domain ◽  
Strand Annealing ◽  
Cellular Compartments

Topoisomerase 3β (Top3β) can associate with the mediator protein Tudor domain-containing protein 3 (TDRD3) to participate in two gene expression processes of transcription and translation. Despite the apparent importance of TDRD3 in binding with Top3β and directing it to cellular compartments critical for gene expression, the biochemical mechanism of how TDRD3 can affect the functions of Top3β is not known. We report here sensitive biochemical assays for the activities of Top3β on DNA and RNA substrates in resolving topological entanglements and for the analysis of TDRD3 functions. TDRD3 stimulates the relaxation activity of Top3β on hypernegatively supercoiled DNA and changes the reaction from a distributive to a processive mode. Both supercoil retention assays and binding measurement by fluorescence anisotropy reveal a heretofore unknown preference for binding single-stranded nucleic acids over duplex. Whereas TDRD3 has a structure-specific binding preference, it does not discriminate between DNA and RNA. This unique property for binding with nucleic acids can have an important function in serving as a hub to form nucleoprotein complexes on DNA and RNA. To gain insight into the roles of Top3β on RNA metabolism, we designed an assay by annealing two single-stranded RNA circles with complementary sequences. Top3β is capable of converting two such single-stranded RNA circles into a double-stranded RNA circle, and this strand-annealing activity is enhanced by TDRD3. These results demonstrate that TDRD3 can enhance the biochemical activities of Top3β on both DNA and RNA substrates, in addition to its function of targeting Top3β to critical sites in subcellular compartments.

scholarly journals Graphene Oxide: A Smart (Starting) Material for Natural Methylxanthines Adsorption and Detection

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4247 ◽  
Author(s):  
Rita Petrucci ◽  
Isabella Chiarotto ◽  
Leonardo Mattiello ◽  
Daniele Passeri ◽  
Marco Rossi ◽  
...  
Keyword(s):  
Electrical Conductivity ◽  
Graphene Oxide ◽  
Nucleic Acids ◽  
Reduced Graphene Oxide ◽  
Electrochemical Sensors ◽  
Enzymatic Digestion ◽  
Biologically Active ◽  
Polar Solvents ◽  
Dna And Rna ◽  
Reduced Graphene

Natural methylxanthines, caffeine, theophylline and theobromine, are widespread biologically active alkaloids in human nutrition, found mainly in beverages (coffee, tea, cocoa, energy drinks, etc.). Their detection is thus of extreme importance, and many studies are devoted to this topic. During the last decade, graphene oxide (GO) and reduced graphene oxide (RGO) gained popularity as constituents of sensors (chemical, electrochemical and biosensors) for methylxanthines. The main advantages of GO and RGO with respect to graphene are the easiness and cheapness of synthesis, the notable higher solubility in polar solvents (water, among others), and the higher reactivity towards these targets (mainly due to – interactions); one of the main disadvantages is the lower electrical conductivity, especially when using them in electrochemical sensors. Nonetheless, their use in sensors is becoming more and more common, with the obtainment of very good results in terms of selectivity and sensitivity (up to 5.4 × 10−10 mol L−1 and 1.8 × 10−9 mol L−1 for caffeine and theophylline, respectively). Moreover, the ability of GO to protect DNA and RNA from enzymatic digestion renders it one of the best candidates for biosensors based on these nucleic acids. This is an up-to-date review of the use of GO and RGO in sensors.

scholarly journals Triazole-Modified Nucleic Acids for the Application in Bioorganic and Medicinal Chemistry

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 628
Author(s):  
Dagmara Baraniak ◽  
Jerzy Boryski
Keyword(s):  
Nucleic Acids ◽  
State Of The Art ◽  
Modified Oligonucleotides ◽  
Synthetic Genes ◽  
Chemically Modified ◽  
Amide Linkage ◽  
Dna And Rna ◽  
Modified Dna ◽  
Modified Nucleic Acids ◽  
Non Coding Rnas

This review covers studies which exploit triazole-modified nucleic acids in the range of chemistry and biology to medicine. The 1,2,3-triazole unit, which is obtained via click chemistry approach, shows valuable and unique properties. For example, it does not occur in nature, constitutes an additional pharmacophore with attractive properties being resistant to hydrolysis and other reactions at physiological pH, exhibits biological activity (i.e., antibacterial, antitumor, and antiviral), and can be considered as a rigid mimetic of amide linkage. Herein, it is presented a whole area of useful artificial compounds, from the clickable monomers and dimers to modified oligonucleotides, in the field of nucleic acids sciences. Such modifications of internucleotide linkages are designed to increase the hybridization binding affinity toward native DNA or RNA, to enhance resistance to nucleases, and to improve ability to penetrate cell membranes. The insertion of an artificial backbone is used for understanding effects of chemically modified oligonucleotides, and their potential usefulness in therapeutic applications. We describe the state-of-the-art knowledge on their implications for synthetic genes and other large modified DNA and RNA constructs including non-coding RNAs.

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