File Name: composition structure and function of nucleic acid .zip
Nucleic acids are molecules that allow organisms to transfer genetic information from one generation to the next.
Alongside proteins , lipids and complex carbohydrates polysaccharides , nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life. The two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. The nucleotides are joined to one another in a chain by covalent bonds known as the phospho-diester linkage between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules A with T and C with G , with hydrogen bonds to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups, pyrimidines and purines.
DNA structure and function
E-mail: Martine. Demeunynck ujf-grenoble. Nucleic acids are the structural supports of genetic material and therefore the key factors in many vital cellular processes. The double-stranded right-handed helix is a regular conformation adopted by both DNA and RNA in cells, but an increasing number of results point to the biological importance of alternative structures such as bulges, hairpins, branched junctions or quadruplexes. Progress in the chemical synthesis of oligonucleotides and in the knowledge of the factors that favour a particular conformation has opened new fields of research in molecular recognition and drug design.
Philippe Belmont was born in Paris in Demeunynck focused on the synthesis and biological properties of heterocyclic heterodimers that recognise specific lesions in DNA. Lehn, Paris, France designing new synthetic vectors for use in gene therapy. In he joined the group of Professor M. He moved then successively to Paris Professor C. His research field is the study of DNA recognition and chemical modifications by specific binders. She was born in in Lille, France. Lhomme to work on the reactivity of nitrenium ion precursors for a PhD in Chemistry.
She spent one post-doctoral year working in the group of Professor J. Her major field of interest is the chemistry of nitrogen heterocycles with the design, synthesis and chemical reactivity of nucleic acid binding molecules.
After a general introduction on DNA and RNA conformations and structures, emphasising their possible biological roles, we will show how the synthesis of oligonucleotides of definite sequence allows the detailed study of particular structures or conformations using a large variety of physical, biochemical and physicochemical methods.
In the second part, the interaction with small molecules and macromolecules will be discussed in terms of biological significance and drug design. Different types of interaction control the structural changes observed in DNA and RNA: the charged phosphate groups of the backbone are mutually repulsive, and the formation of hydrogen bonds between bases and strong stacking interaction between the flat surfaces of the base pairs are implicated in the formation of multistranded structures double- or triple-stranded helices, quadruplexes The different conformations are not static entities.
Each nucleotide has its own dynamics, thus conferring local motion on the helix in addition to the global motion of the macromolecule. As shown in Fig. The base pairs are displaced off-axis. B-DNA is slimmer, more elongated with base planes essentially perpendicular to the helix axis, with a narrow minor groove and a wide major groove. The base pairs sit directly on the axis so that the major and minor grooves are of equal depth.
For A- and B-conformations, the glycosylic bond is in the anti conformation. The major groove is completely flattened out on the surface of the molecule and the minor groove is very deep. The characteristic zigzag chain path in Z-DNA arises from the alternation of syn and anti conformations at guanine and cytosine respectively, which causes a local chain reversal and produces a helical repeat consisting of two successive bases, purine plus pyrimidine.
To do so, the purine residues rotate around their glycosylic bonds, from anti to syn positions and for the pyrimidine nucleosides, both the bases and the sugars rotate to produce the characteristic zigzag backbone conformation.
The mechanism of this conversion is far from obvious and has received little attention compared to the physical and chemical studies of the Z-conformation itself. It should be noted that the position of the imidazole ring of guanine is profoundly affected by the conformation. This difference in accessibility accounts for the difference in reactivity of the two forms of the macromolecule.
In aqueous solution and in cells, DNA is essentially in B-form. Nevertheless, the existence of the Z-conformation in vivo and its biological role is still an intensive area of research. Most of the work dealing with in vivo studies of Z-DNA has been reviewed by Herbert and Rich; 5 the major findings are the formation and stabilisation of Z-DNA by negative supercoiling. Formation of the Z-conformation unwinds DNA, thus relaxing the supercoils, which is a thermodynamically favoured process.
It has been proposed that the energy necessary to form and stabilise Z-DNA in vivo can be generated during the transcription process. Curvature is another significant feature of double-stranded DNA. The importance of curvature in DNA condensation and in the expression of genetic information justifies wide interest in this structural feature. It has been suggested that short runs of adenines, or A-tracts, separated by mixed sequences, produce substantial curvature of DNA.
This hypothesis is the basis of sequence-directed curvature of DNA. Different models have been proposed to explain curvature, mostly based on interruption of the B-form DNA by an A-tract that adopts a non-B helix structure.
In DNA, bulge formation may provoke mutations due to replication or transcription errors. Cruciforms contain three components: the loops, the stems and the four-way junction Fig. The stems are normally fully base paired in the B-conformation and are not subjected to supercoiling. The loops are single-stranded structures positioned at the end of each stem that contain two or more unpaired bases.
Cruciform extrusion and stabilisation require DNA supercoiling, and result in the relaxation of one negative supercoil per Two mechanisms S- and C-pathways account for the cruciform extrusion.
A mechanism of branch migration then forms the cruciform structure. Holliday junctions occur between two DNA regions of homologous sequences. This sequence identity allows one strand to base pair either with its original complementary strand or with a complementary segment of the second duplex. To be formed, Holliday junctions require the close proximity of the two helices that lead to groove—backbone interactions DNA self-fitting.
The four-way junctions are involved in major biological events both in prokaryotes and in eukaryotes as reviewed in detail by Sinden 2 and Pearson. Holliday junctions are formed during chromosome recombination, a major genetic process involved in gene expression and repair, which allows DNA to exchange sequences. Three- and four-way junctions are also common in RNA and constitute the key elements for the folding into the three-dimensional structures responsible for the specific biological and catalytic activities of RNAs.
In natural DNA, supercoiling is the major factor influencing Z-formation. At the oligonucleotide level, interconversion between right-handed and left-handed helices is dependent on environmental factors such as the presence of metal ions, polyamines or organic solvents and upon the presence of modifications on the bases. These factors have been extensively discussed in recent reviews 2,9 and the main points are outlined here. Introduction of a bulky substituent, bromine or methyl group, at position 8 of guanines stabilises the Z-conformation since steric hindrance forces the deoxyribose to the syn position.
Introduction of a methyl group or bromine at C5 of cytosine also favours the Z-conformation. The presence of a methyl group at position 5 of cytosine has been extensively studied as it stabilises the Z-conformation under physiological conditions, suggesting the biological interest of these structures.
Indeed, poly dG—dm 5 C. Another feature of Z-DNA is that phosphate groups on opposite strands approach much closer than in B-DNA and therefore any factor that will reduce the phosphate—phosphate repulsion shielding effect will favour and stabilise the Z-form. Typical salt conditions necessary to induce the Z-conformation in poly dG—dC. The effect is more pronounced with poly dG—dm 5 C. Polyamines have also been shown to stabilise the Z-conformation. The effect is strongly dependent on the sequence of the oligonucleotide and the nature of the polyamine.
Poly dG—dm 5 C. The influence of drugs on the B—Z equilibrium has also been studied. Most of the drugs that intercalate between DNA base pairs for example, proflavine, ethidium bromide, and the anticancer agent daunomycin shown in Fig. This transition can be related to a higher affinity of the drugs for the B-form that progressively shifts the equilibrium in favour of B-DNA. An interesting behaviour was observed for poly dG—dC.
Gel electrophoresis is a very sensitive and non-perturbing technique that appeared to be a method of choice to study structural changes of pseudo-cruciforms. A stable junction is characterised by a much slower electrophoretic migration compared to linear sequences and this migration is dependent on the position of the junction relative to the ends of the arms. The conformations of the four-way junctions are highly influenced by the presence of cations.
From these experiments, a structure was proposed for the Holliday junction, with an X-like conformation resulting from collinear association of two helices. Upon excitation of the donor, energy is transferred to the acceptor through dipolar interaction between the two transition moments; the efficiency of the transfer is dependent on the distance between donor and acceptor fluorophores.
Different donor—acceptor molecules can be used. Comparison of the efficiencies of FRET allows the determination of the preferred conformations. The data thus obtained fully confirmed the conformations proposed earlier. The oligonucleotides used for the early electrophoresis measurements contained about 80 nucleotides and were too long for NMR methodology. Therefore for the NMR studies, shorter oligonucleotides were synthesised, with 16 residues per strand 64 for the full junction and then later a stable four-way junction with 38 nucleotides was prepared and studied.
Proton NMR data confirmed the stacked X-conformation and indicated that one single isomer was preferred. Another interesting finding was that full Watson—Crick base pairing was preserved at the junction site. It has been shown that guanine rich sequences form quadruplexes with different topologies and strand orientation depending on the sequence.
Different types of quadruplexes, such as dimeric, tetrameric or intramolecular structures, have been reported Fig. One of the most extensively studied DNA sequences, d G 4 T 4 G 4 , derived from the Oxytricha nova telomere, forms dimeric quadruplex structures [d G 4 T 4 G 4 ] 2 with four guanine-quartets.
However, the structures obtained by X-ray crystallography and NMR spectroscopy display different conformations and folding topologies. Other nucleic bases might also form quadruplexes as A- or T-quadruplexes have been recently reported. The interaction of neocarzinostatin chromophore with bulged DNA was studied in detail by Goldberg and co-workers 23 Neocarzinostatin Fig. As with other members of the ene-diyne family, the neocarzinostatin chromophore is activated by the formation of a biradical species that induces DNA cleavage by hydrogen abstraction.
The specific interaction of the active form of the drug with a bulge appeared to modify its chemical behaviour. The cleavage efficiency was enhanced and the reaction led to a new drug product. A detailed NMR study of the complex formed between the drug and a bulge revealed a perfect fit between the active form of the drug and the bulge. Surprisingly, while a number of DNA bulges have been shown to interact with neocarzinostatin, the drug cleaves RNA bulges very poorly. These experiments also point out the necessity of a bulge-specific drug binding for efficient cleavage.
Different classes of compounds have been shown to bind specific sites such as bulges and hairpins of structured RNAs. These include, for example, small organic and inorganic ligands, short peptides. This area has been reviewed recently. These molecules were shown to interact with a bulge containing RNA.
What Is the Importance of Nucleic Acids?
E-mail: Martine. Demeunynck ujf-grenoble. Nucleic acids are the structural supports of genetic material and therefore the key factors in many vital cellular processes. The double-stranded right-handed helix is a regular conformation adopted by both DNA and RNA in cells, but an increasing number of results point to the biological importance of alternative structures such as bulges, hairpins, branched junctions or quadruplexes. Progress in the chemical synthesis of oligonucleotides and in the knowledge of the factors that favour a particular conformation has opened new fields of research in molecular recognition and drug design. Philippe Belmont was born in Paris in
Deoxyribonucleic acid DNA is a nucleic acid that contains the genetic instructions for the development and function of living things. It is often compared to a blueprint, since it contains the instructions to construct other components of the cell, such as proteins and RNA molecules. The DNA segments that carry genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the expression of genetic information. In eukaryotes such as animals and plants, DNA is stored inside the cell nucleus, while in prokaryotes such as bacteria and archaea, the DNA is in the cell's cytoplasm. Other proteins such as histones are involved in the packaging of DNA or repairing the damage to DNA that causes mutations.
Nucleic acids are vital for cell functioning, and therefore for life. Together, they keep track of hereditary information in a cell so that the cell can maintain itself, grow, create offspring and perform any specialized functions it's meant to do. Nucleic acids thus control the information that makes every cell, and every organism, what it is. Nucleic acids are a macromolecule found in cells. Like proteins and polysaccharides, the other macromolecules, nucleic acids are long molecules made up of many similar linked units. Each is made up of four different nucleotides--adenine, cytosine, guanine, and thymine in DNA, and adenine, cytosine, guanine and uracil in RNA.
determination of structure–function relationships between DNA. and RNA Adenine and guanine are double-ring structures termed purines.
DNA structure and function
Nucleic acid , naturally occurring chemical compound that is capable of being broken down to yield phosphoric acid , sugars, and a mixture of organic bases purines and pyrimidines. Nucleic acids are the main information-carrying molecules of the cell , and, by directing the process of protein synthesis , they determine the inherited characteristics of every living thing. DNA is the master blueprint for life and constitutes the genetic material in all free-living organisms and most viruses. RNA is the genetic material of certain viruses, but it is also found in all living cells, where it plays an important role in certain processes such as the making of proteins.
He reported finding a weakly acidic substance of unknown function in the nuclei of human white blood cells, and named this material "nuclein". A few years later, Miescher separated nuclein into protein and nucleic acid components. In the 's nucleic acids were found to be major components of chromosomes, small gene-carrying bodies in the nuclei of complex cells.
The code within our DNA provides directions on how to make proteins that are vital for our growth, development, and overall health. DNA stands for deoxyribonucleic acid. DNA is a vitally important molecule for not only humans, but for most other organisms as well. But what does DNA actually do? The complete set of your DNA is called your genome.
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