Chemistry of Nucleic Acids

Having identified the genetic material as the nucleic acid DNA (or RNA), we proceed to examine the chemical structure of these molecules. Generally nucleic acids are a long chain or polymer of repeating subunits called nucleotides. Each nucleotide subunit is composed of three parts: a nitrogenous base, a five carbon sugar (pentose) and a phosphate group.

There are two types of nucleic acids depending on the type of pentose sugar. Those containing deoxyribose sugar are called Deoxyribo Nucleic Acid (DNA) and those with ribose sugar are known as Ribonucleic Acid (RNA). DNA is found in the nucleus of eukaryotes and nucleoid of prokaryotes. The only difference between these two sugars is that there is one oxygen atom less in deoxyribose.

The bases are nitrogen containing molecules having the chemical properties of a base (a substance that accepts H+ ion or proton in solution). DNA and RNA both have four bases (two purines and two pyrimidines) in their nucleotide chain. Two of the bases, Adenine (A) and Guanine (G) have double carbon–nitrogen ring structures and are called purines. The bases, Thymine (T), Cytosine (C) and Uracil (U) have single ring structure and these are called pyrimidines. Thymine is unique for DNA, while Uracil is unique for RNA.

It is derived from phosphoric acid (H3PO4), has three active OH- groups of which two are involved in strand formation. The phosphate functional group (PO4) gives DNA and RNA the property of an acid (a substance that releases an H+ ion or proton in solution) at physiological pH, hence the name nucleic acid. The bonds that are formed from phosphates are esters. The oxygen atom of the phosphate group is negatively charged after the formation of the phosphodiester bonds. This negatively charged phosphate ensures the retention of nucleic acid within the cell or nuclear membrane.

The nitrogenous base is chemically linked to one molecule of sugar (at the 1-carbon of the sugar) forming a nucleoside. When a phosphate group is attached to the 5’ carbon of the same sugar, the nucleoside becomes a nucleotide. The nucleotides are joined (polymerized) by condensation reaction to form a polynucleotide chain. The hydroxyl group on the 3’ carbon of a sugar of one nucleotide forms an ester with the phosphate of another nucleotide. The chemical bonds that link the sugar components of adjacent nucleotides are called phosphodiester bond (5’ 3’), indicating the polarity of the strand.

The ends of the DNA or RNA are distinct. The two ends are designated by the symbols 5’ and 3’. The symbol 5’ refers to carbon in the sugar to which a phosphate (PO4) functional group is attached. The symbol 3’ refers to carbon in the sugar to which hydroxyl (OH) functional group is attached. In RNA, every nucleotide residue has an additional –OH group at 2’ position in the ribose. Understanding the 5’ 3’ direction of a nucleic acid is critical for understanding the aspects of replication and transcription.

Based on the X - ray diffraction analysis of Maurice Wilkins and Rosalind Franklin, the double helix model for DNA was proposed by James Watson and Francis Crick in 1953. The highlight was the base pairing between the two strands of the polynucleotide chain. This proposition was based on the observations of Erwin Chargaff that Adenine pairs with Thymine (A = T) with two hydrogen bonds and Guanine pairs with Cytosine (G ≡ C) with three hydrogen bonds. The ratios between Adenine with Thymine and Guanine with Cytosine are constant and equal. The base pairing confers a unique property to the polynucleotide chain. They are said to be complementary to each other, that is, if the sequence of bases in one strand (template) is known, then the sequence in the other strand can be predicted. The salient features of DNA structure has already been dealt in class XI.