Chemistry

DNA is a nucleic acid which is pervasive in nature and whose main function is to carry genetic information. As the hereditary material, it has certain distinctive physicochemical, topological, thermodynamic and electrical properties which enable it to perform this function with stunning accuracy. For instance, these properties enable the DNA molecule to remain stable, to replicate and to carry the billions of genes that code for proteins and determine the phenotype while at the same time being able to fit in the cell. This essay looks at the structure of the DNA in an in-depth manner. The various features of DNA are considered and correlations made with its biochemical role in the body.

The Primary, Secondary and Tertiary Structure of DNA
DNA is made up of 2 polynucleotide strands. These strands are not only anti-parallel but they are also complementary. The polynucleotide strands are composed of a sugar-phosphate backbone on the outside, and nucleotide bases on the inside. As such, the primary structure of DNA is made up of sequences of nucleotides. The nucleotide bases which flank the sugar-phosphate backbone are either purine or pyridine bases. The 4 basic bases include adenine (A), thymine (T), cytosine (C) and guanine (G). Adenine and guanine are known as the purines while cytosine and guanine are known as pyrimidines. The purines have 2 rings while the pyrimidines are made up of only 1 ring. The complementarity of the polynucleotide strands occurs because of the specificity of base pairing. Adenine pairs with thymine while cytosine pairs with guanine. However, non-conventional base pairing where adenine pairs with cytosine and guanine with adenine has been observed. This occurrence has been attributed to the wobble effect. In some instances, some DNA molecules have unique bases. DNA may be circular or linea.

Figure  SEQ Figure  ARABIC 1 Base pairing in DNA. A pairs with T and C pairs with G.
The 2 strands are held together by hydrogen bonds that form between the complimentary base pairs. Two H bonds reinforce the A-T pairs while 3 H bonds reinforce the G-C pairs. This is a very important feature with significant ramifications on the biochemical role of DNA. For one, the base composition determines the melting point of the DNA. Since the A-T pairing is fortified by only 2 H bonds, DNA which is rich in these 2 bases has a lower melting point. On the other hand, the G-C bonds are fortified by 3 H bonds therefore DNA that is rich in GC has a higher melting point. When DNA is subjected to temperatures above the melting point, the H bonds are broken and the 2 strands come apart. In other words, the double stranded DNA is converted into the single stranded form.

Figure  SEQ Figure  ARABIC 2 Diagram showing the secondary structure of DNA. The nucleotides are made up of the deoxyribose sugar, a purine or pyrimidine base and a phosphate group. The nucleotides are located inside the sugar-phosphate backbone. A pairs with T and G with C and the 2 polynucleotide strands are kept together by weak hydrogen bonds

When the temperature goes below the melting point, the H bonds between the complementary bases on the different strands are re-established and the double stranded form of DNA is reformed. In other words, the DNA re-anneals. This property also has an effect on the biochemical role of DNA as the two strands must be separated before replication or transcription can occur and proteins necessary for cellular functions to be produced. The relatively weak H bonds make it easy for enzymes known as helicases to unwind the DNA during replication and transcription and this enhances the efficiency of the 2 processes. DNA absorbs light at 260nm. When the DNA is denatured, the absorbance of light increases. The implication is that single stranded DNA has a higher absorbance than the double stranded form.
   
The sugar moiety in DNA is deoxyribose sugar. This is a pentose sugar with a H at the 2 position. In contrast, the other nucleic acid which is RNA has a hydroxyl (OH) group at the same position. The H group at the 2 position on the DNA molecule makes it to be more stable and this is important for the molecule to be able to carry out its biochemical roles.

The sugar and phosphate groups of adjoining nucleotides are connected with covalent phosphodiester bonds. These phosphodiester bonds are stronger than the H bonds between the different bases. The phosphate groups are negatively charged and this confers a net negative charge on the entire DNA molecule. As will be seen shortly, this is very important for DNA since it enables the DNA to be highly compacted so that it can fit into the cell without compromising its ability to carry lots of information through the billions of genes it carries. The net negative charge also has a significant effect on the behaviour of the DNA in solution. In solution, DNA can exist in 3 different forms. The most common form of DNA is B DNA (1, 2). The other forms of DNA which have been observed in solution are A DNA and Z DNA. The different forms of DNA will be considered shortly.

In terms of its secondary structure, DNA exists in a double helical form. The 2 polynucleotide strands wind about a common axis, creating a right-handed double helix. There are alternate grooves on the double helices and these are called the major and minor grooves. The major groove is 12 while the minor groove is 6. The major grove is also deeper than the minor groove. These grooves play an important role in many biochemical processes. For instance, the minor groove serves as an attachment site for DNase 1. The major groove is used as an attachment site by proteins which regulate the expression of genes. These regulatory proteins are defined by their structural motifs and include the helix-turn-helix, helix-loop-helix, leucine-zipper, steroid hormone, homeodomain and zinc finger motifs. They bind onto the major groove and control many cellular processes. As can be seen therefore, the unique chemical composition of the grooves enables proteins to be expressed in a precise manner as it confers sites for adherence of the regulatory proteins.

Different forms of DNA
As implied before, the commonest form of DNA is B DNA. This form of DNA consists of 10 base pairs per turn. Since each complete turn is 360, the rotation per base pair is 36. Generally, the B DNA is long and narrow in shape and has a diameter of 1.9 nm. The distance between the bases is 0.34nm. B DNA has no unique bases and occurs when there is plenty of water in the cell surroundings (92 water). B DNA spirals to form major and minor grooves and these groves are important for proper cellular function as DNA binding proteins attach to these grooves and help to regulate the expression of genes.

DNA can also exist as A DNA when there is less water in the surroundings (75 water). Even though A DNA has not been isolated under physiological conditions, it is a right handed helix with 11 base pairs per turn. Thus, the rotation per base pair is 32.7. The distance between the bases in A DNA is 0.26nm, the diameter is 2.3 nm and the overall shape is short and wide.
Z DNA is formed by alternating purine and pyrimidine bases. Unlike B and A DNA, Z DNA is a left handed helical structure with 12 base pairs per turn and a rotation of -30 per base pair. The distance between the base pairs is 0.37nm and the overall shape is elongated and narrow. This form of DNA also has only 1 deep groove. B DNA can interchange to the Z DNA if it is methylated at the 5 carbon or whenever negative supercoiling occurs.

In terms of its tertiary structure, DNA is supercoiled and preformed by higher chromatin folding. Supercoiling can either be negative or positive depending on whether the double helices have been underwound or overwound. B DNA usually manifests negative supercoiling and this is very important for proper cellular function since molecules that are negatively supercoiled can be easily unwound to enable replication and transcription to occur. Conversely, positively supercolied molecules are not easily unwound.

It was also mentioned before that the negative charge of the DNA is important for compaction. This is especially so in eukaryotes because DNA is wound around positively charged histone proteins which are rich in the basic amino acids and especially lysine. There are 5 types of histone proteins and these are H2A, H2B, H3, H4 and H1. Two units each of H2A, H2B, H3 and H4 associate to form a histone octamer onto which the DNA is wound. H1 stabilizes the formation. The linkage between DNA and the histones is very strong due to the attraction between the negative charges on the DNA and positive charges on the histones. Having been wound onto the histones, the DNA is further folded onto itself many times. This not only helps to compact the DNA and make it fit into the cell but also has significant ramifications on the expression of genes and consequently the production of proteins. It means that the strong bonds between the DNA and histones must be weakened so that the nucleotide bases are exposed for replication and transcription to occur and thereafter re-established after these processes are over. In a sense, it plays a vital role in biochemical processes as it prevents the constitutive replication and expression of genes and allows these to occur if and only if there is a need as indicated by specific mechanisms.

DNA exists as a double stranded helix and may either be right handed as in A and B DNA or left handed as in Z DNA. The helices are made up of a sugar-phosphate backbone on the outside and nucleotides on the inside. The nucleotides are made up of the deoxyribose sugar, a purine or pyrimidine base and a phosphate group. A pairs with T and G with C and the 2 polynucleotide strands are kept together by weak hydrogen bonds. Major and minor grooves innervate the helices and the molecule is negatively charged.  In conclusion, it can be stated that DNA is a highly complex molecule with several distinctive physicochemical, structural, thermodynamic and electrical features that are important for its role as a carrier of genetic information.