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2.1.2
The structure of nucleic acids

Nucleic Acids

Nucleic acids are polymers of mononucleotides. Condensation reactions are involved in the formation of both the mononucleotides themselves and polynucleotides. Two important nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). 1. Deoxyribonucleic acid (DNA) DNA consists of two strands twisted into a double helical configuration. Each strand is a polymer of mononucleotides. A single DNA mononucleotide has three parts: a phosphate group, a sugar (deoxyribose) and a nitrogen-containing base. Phosphate group:

Deoxyribose (a 5-carbon sugar or pentose):

Nitrogenous base:

These three groups are covalently bonded via condensation reactions thus: A nucleotide

abbreviation:

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These nucleotides polymerise via condensation reactions to form a long chain called a polynucleotide or nucleic acid. The sugar group of one nucleotide covalently links to the phosphate group of the next. The bond thus formed is known as a phosphodiester bond. A sugar-phosphate backbone is formed with the bases sticking out. The end of the chain with the free phosphate group is known as the 5 end because the phosphate group is linked to C-5 on the deoxyribose molecule. The end of the chain with the uncombined sugar is known as the 3 end because C-3 of the sugar is not linked to the phosphate group of another nucleotide. We now have to consider the second nucleic acid chain which lies alongside and parallel to the first: The two sugar-phosphate backbones form the outside of the double helix and the bases of the two strands project towards one another and pair up. The sugar-phosphate backbones run in opposite directions. They are said to be antiparallel. The base adenine forms weak bonds with thymine on the opposite chain. Guanine forms weak bonds with cytosine. There are stereochemical reasons for this complementary base pairing: (i) A double ring structure always pairs with a single ring. i.e. purine with pyrimidine. Any other combination would lead to narrowing or bulging of the DNA and regular helices would not form. Two hydrogen bonds form spontaneously between A and T. Three hydrogen bonds form spontaneously between G and C.

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(ii)

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The bases are attached horizontally to the backbone and lie inside the double helix stacked up like stair steps. The two paired chains spontaneously fold into a double helix.

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DNA Replication Each strand of the double helix contains the information necessary to make its complementary strand. An enzyme called helicase catalyses the unwinding of the helix and initiates separation of the two strands. The enzyme, DNA polymerase, is also involved in the separation of the two strands. There are plenty of free nucleotides in the nucleus each consisting of the pentose sugar, deoxyribose, a base and three phosphates. When a free nucleotide meets its complementary base on the exposed DNA, hydrogen bonds are formed between them. As the DNA helix opens further, more free nucleotides are attracted to the original strands. DNA polymerase links adjacent free nucleotides knocking off extra phosphates. i.e. DNA polymerase catalyses the polymerisation of the sequence of free nucleotides to make new DNA strands. DNA polymerase can only build up strands in the 5 to 3 direction. The 3 to 5 strand is built up in short sections in the 5 to 3 direction. These sections are then joined together by the enzyme, DNA ligase. Because its synthesis takes slightly longer, the discontinuously synthesized daughter strand is known as the lagging strand while the continuously synthesized strand is called the leading strand.

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Two new double helices are produced. Each contains one original strand and one new strand. Hence replication of DNA is said to be semi-conservative. The effect of DNA helicase and DNA polymerase running along the double helix is to open up a replication fork. Replication forks moving in opposite directions from a replication origin form a replication bubble. In the relatively small loop of DNA that is the bacterial chromosome, there is one replication origin. There are many replication origins in a eukaryotic chromosome:

2 replication forks = replication bubble

How replication bubbles merge (Arrows indicate the direction of movement of the replication forks)

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The sequence of amino acids (primary structure) in a protein is of fundamental importance to that proteins higher order structure and hence its function. The sequence of DNA bases determines the sequence of amino acids in a protein. A structural gene is a sequence of DNA nucleotides that codes for a polypeptide. Ribonucleic acid is involved in bringing about the translation of the DNA code into a sequence of amino acids. 2. Ribonucleic acid (RNA) DNA - RNA similarities: Both are polymers of nucleotides. Both involve strands which comprise a sugar-phosphate backbone with a series of bases attached. DNA - RNA differences: DNA (i) sugar

RNA

deoxyribose (ii) (iii) double-stranded more than 1 million nucleotides in any one strand adenine guanine cytosine thymine

ribose single-stranded (usually) 50 - 1000 nucleotides i.e. much shorter In place of thymine, RNA has uracil (U) which, like thymine, is complementary to adenine (thymine has an extra - CH3 group on the single ring structure)

(iv) base

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There are three types of RNA found in cells, all of which are involved in protein synthesis: (i) Messenger RNA (mRNA) is a long single-stranded molecule, of up to thousands of nucleotides, which is formed into a helix. It is manufactured in the nucleus by complementary base-pairing against a DNA template. It enters the cytoplasm where it associates with ribosomes and acts as a template for protein synthesis. Each group of three bases on the mRNA dictates the position of a particular amino acid in a polypeptide chain. Such a triplet of bases is called an mRNA codon. (ii) Transfer RNA (tRNA) is a small molecule and is single-stranded. It forms a cloverleaf shape with one end of the chain ending in a cytosine- cytosine-adenine sequence. An amino acid will attach itself at this point. There are at least 20 types of tRNA, each one carrying a different amino acid. At an intermediate point along the strand and projecting from a loop of the molecule is a sequence of three bases called the anticodon. The anticodon determines which amino acid is attached to the tRNA and is attracted by complementary base pairing to an mRNA codon. Thus an amino acid is brought into position along the mRNA.

(iii) Ribosomal RNA (rRNA) is a large, complex molecule made up of both double and single helices. It makes up more than half the mass of ribosomes. A ribosome is a large body which provides a protective environment for protein synthesis and also contains necessary enzymes. The base sequence of rRNA is similar in all organisms. Like mRNA, rRNA and tRNA are both manufactured in the nucleus by complementary base-pairing against DNA templates and function in the cytoplasm.

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