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In this lecture educator explains about structure of nucleic acid. Nucleic acids are molecules that allow organisms to transfer genetic information from one generation to the next. There are two types of nucleic acids: deoxyribonucleic acid (better known as DNA) and ribonucleic acid (better known as RNA).
Discovery and Presence: A nucleic acid is a long molecule made up of smaller molecules called nucleotides. Nucleic acids were discovered in 1868, when twenty-four-year-old Swiss physician Friedrich Miescher isolated a new compound from the nuclei of white blood cells. This compound was neither a protein nor lipid nor a carbohydrate; therefore, it was a novel type of biological molecule. Miescher named his discovery "nuclein," because he had isolated it from the nuclei of cells.
Structure of Nucleic Acids: Nucleic acids are composed of nucleotide monomers linked together. Nucleotides contain three parts:
- A Nitrogenous Base
- A Five-Carbon Sugar
- A Phosphate Group
Types of Nucleic Acids: Nucleic acids are of two types namely, DNA and RNA. DNA is Deoxy Ribonucleic acid, it contains deoxy ribose sugar, phosphate and bases like adenine, guanine, thymine and cytosine whereas RNA, ribonucleic acid, contains ribose sugar, phosphate and bases like
Artificial nucleic acids include peptide nucleic acid (PNA), Morpholino and locked nucleic acid (LNA), as well as glycol nucleic acid (GNA) and threose nucleic acid (TNA). Each of these is distinguished from naturally occurring DNA or RNA by changes to the backbone of the molecule.
The DNA is the biological molecule that stores all the genetic information of the cell (in some virus’s RNA may function as the molecule that stores the genetic information). Everything that the cells has to do, at what time in its life cycle, and how it has to do it is determined by the information contained in the DNA molecule. In addition, DNA functions as the molecule that carries on the genetic information from parent to offspring.
RNA is made when the complex biochemical decodification machinery of the cell acts on the DNA to extract the information needed for a particular function. RNA is a key factor for protein synthesis. RNA is responsible for transferring the information contained in the DNA to make a particular protein needed in a specific process for a specific function.
Primary Structure of Nucleic Acids
Primary structure of DNA is formed by the covalent backbone consisting of deoxyribo nucleotides linked to each other by phosphodiester bonds. DNA’s are long chains of nucleotide units or polydeoxyribonucleotides. The substrates for polymerization are nucleoside triphosphates, but the repeating unit or monomer, of a nucleic acid is a monophosphate. During polymerization, the 3’-OH group of the terminal nucleotide residue in the existing chain makes a nucleophilic attack upon the alpha phosphate of the incoming nucleoside triphosphate to form 5’3’ phosphodiesterbond. This reaction is catalyzed by DNA polymerase. Serial polymerization generates long polymers variously called chains or strands, containing an invariant sugar-phosphate backbone with 5’3’ polarity and projecting nitrogenous base.
Structure of RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation, and expression of genes. RNA and DNA are nucleic acids, and, along with lipids, proteins and carbohydrates, constitute the four-major macromolecule essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA it is more often found in nature as a single-strand folded onto itself, rather than a paired double-strand. Cellular organisms use messenger RNA (mRNA) to convey genetic information (using the letters G, U, A, and C to denote the nitrogenous bases guanine, uracil, adenine, and cytosine) that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.
Some RNA molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. One of these active processes is protein synthesis, a universal function where RNA molecules direct the assembly of proteins on ribosomes. This process uses transfer RNA (tRNA) molecules to deliver amino acids to the ribosome, where ribosomal RNA (rRNA) then links amino acids together to form proteins.
Secondary and Tertiary Structure of DNA
Secondary structure is the set of interactions between bases, i.e., which parts of strands are bound to each other. In DNA double helix, the two strands of DNA are held together by hydrogen bonds. The nucleotides on one strand base pairs with the nucleotide on the other strand. The secondary structure is responsible for the shape that the nucleic acid assumes. The bases in the DNA are classified as purines and pyrimidines. The purines are adenine and guanine. Purines consist of a double ring structure, a six membered and a five-membered ring containing nitrogen. The pyrimidines are cytosine and thymine. It has a single ringed structure, a six-membered ring containing nitrogen. A purine base always pairs with a pyrimidine base (guanine (G) pairs with cytosine (C) and adenine (A) pairs with thymine (T) or uracil (U)). DNA's secondary structure is predominantly determined by base-pairing of the two polynucleotide strands wrapped around each other to form a double helix. Although the two strands are aligned by hydrogen bonds in base pairs, the stronger forces holding the two strands together are stacking interactions between the bases. These stacking interactions are stabilized by Van der Waals forces and hydrophobic interactions, and show a large amount of local structural variability. There are also two grooves in the double helix, which are called major groove and minor groove based on their relative size.
Tertiary structure refers to the locations of the atoms in three-dimensional space, taking into consideration geometrical and steric constraints. It is a higher order than the secondary structure, in which large-scale folding in a linear polymer occurs and the entire chain is folded into a specific 3-dimensional shape. There are 4 areas in which the structural forms of DNA can differ.
- Handedness – right or left
- Length of the helix turn
- Number of base pairs per turn
- Difference in size between the major and minor grooves
The tertiary arrangement of DNA's double helix in space includes B-DNA, A-DNA and Z-DNA.
B-DNA is the most common form of DNA in vivo and is a more narrow, elongated helix than A-DNA. Its wide major groove makes it more accessible to proteins. On the other hand, it has a narrow minor groove. B-DNA's favored conformations occur at high water concentrations; the hydration of the minor groove appears to favor B-DNA. B-DNA base pairs are nearly perpendicular to the helix axis. The sugar pucker which determines the shape of the a-helix, whether the helix will exist in the A-form or in the B-form, occurs at the C2'-endo.
A-DNA, is a form of the DNA duplex observed under dehydrating conditions. It is shorter and wider than B-DNA. RNA adopts this double helical form, and RNA-DNA duplexes are mostly A-form, but B-form RNA-DNA duplexes have been observed. In localized single strand dinucleotide contexts, RNA can also adopt the B-form without pairing to DNA. A-DNA has a deep, narrow major groove which does not make it easily accessible to proteins. On the other hand, its wide, shallow minor groove makes it accessible to proteins but with lower information content than the major groove. Its favoured conformation is at low water concentrations. A-DNAs base pairs are tilted relative to the helix axis, and are displaced from the axis. The sugar pucker occurs at the C3'-endo and in RNA 2'-OH inhibits C2'-endo conformation. Long considered little more than a laboratory artifice, A-DNA is now known to have several biological functions.
Z-DNA is a relatively rare left-handed double-helix. Given the proper sequence and superhelical tension, it can be formed in vivo but its function is unclear. It has a more narrow, more elongated helix than A or B. Z-DNA's major groove is not really a groove, and it has a narrow minor groove. The most favored conformation occurs when there are high salt concentrations. There are some base substitutions, but they require an alternating purine-pyrimidine sequence. The N2-amino of G H-bonds to 5' PO, which explains the slow exchange of protons and the need for the G purine. Z-DNA base pairs are nearly perpendicular to the helix axis. Z-DNA does not contain single base-pairs but rather a GpC repeat with P-P distances varying for GpC and CpG. On the GpC stack there is good base overlap, whereas on the CpG stack there is less overlap. Z-DNA's zigzag backbone is due to the C sugar conformation compensating for G glycosidic bond conformation. The conformation of G is syn, C2'-endo and for C it is anti, C3'-endo.
A linear DNA molecule having free ends can rotate, to adjust to changes of various dynamic processes in the cell, by changing how many times the two chains of its double helix twist around each other. Some DNA molecules are circular and are topologically constrained. More recently circular RNA was described as well to be a natural pervasive class of nucleic acids, expressed in many organisms. A covalently closed, circular DNA (also known as cccDNA) is topologically constrained as the number of times the chains coiled around one other cannot change. This cccDNA can be supercoiled, which is the tertiary structure of DNA. Supercoiling is characterized by the linking number, twist and writhe. The linking number (Lk) for circular DNA is defined as the number of times one strand would have to pass through the other strand to completely separate the two strands. The linking number for circular DNA can only be changed by breaking of a covalent bond in one of the two strands. Always an integer, the linking number of a cccDNA is the sum of two components: twists (Tw) and writhes (Wr).
Twists are the number of times the two strands of DNA are twisted around each other. Writhes are number of times the DNA helix crosses over itself. DNA in cells is negatively supercoiled and has the tendency to unwind. Hence the separation of strands is easier in negatively supercoiled DNA than in relaxed DNA. The two components of supercoiled DNA are solenoid and plectonemic. The plectonemic supercoil is found in prokaryotes, while the solenoidal supercoiling is mostly seen in eukaryotes.
In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes. Chromosomes are not visible in the cell’s nucleus—not even under a microscope—when the cell is not dividing. However, the DNA that makes up chromosomes becomes more tightly packed during cell division and is then visible under a microscope. Most of what researchers know about chromosomes was learned by observing chromosomes during cell division. Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or “arms.” The short arm of the chromosome is labeled as “p arm.” The long arm of the chromosome is labeled as “q arm.” The location of the centromere on each chromosome gives the chromosome its characteristic shape, and can be used to help describe the location of specific genes.
Nucleosome is a section of DNA that is wrapped around a core of proteins. Inside the nucleus, DNA forms a complex with proteins called chromatin, which allows the DNA to be condensed into a smaller volume. When the chromatin is extended and viewed under a microscope, the structure resembles beads on a string. Each of these tiny beads is a called a nucleosome and has a diameter of approximately 11 nm. The nucleosome is the fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a histone octamer. Each histone octamer is composed of two copies each of the histone proteins H2A, H2B, H3, and H4.
Chromosomes has following subtypes:
- Metacentric chromosomes have the centromere in the centre, such that both sections are of equal length. Human chromosome 1 and 3 are metacentric.
- Submetacentric chromosomes have the centromere slightly offset from the centre leading to a slight asymmetry in the length of the two sections. Human chromosomes 4 through 12 are submetacentric.
- Acrocentric chromosomes have a centromere which is severely offset from the centre leading to one very long and one very short section. Human chromosomes 13,15, 21, and 22 are acrocentric.
- Telocentric chromosomes have the centromere at the very end of the chromosome. Humans do not possess telocentric chromosomes, but they are found in other species such as mice.