A Nucleic Acid Strand Is a Linear Polymer with End-to-End Directionality

In all organisms, DNA and RNA are each made up of only four different nucleotides. Recall from Chapter 2 that all nucleotides consist of an organic base linked to a five-carbon sugar that has a phosphate group attached to the 5′ carbon. In RNA, the sugar is ribose; in DNA, deoxyribose (see Figure 2-16). The nucleotides used in synthesis of DNA and RNA contain five different bases. The bases adenine (A) and guanine (G) are purines, which contain a pair of fused rings; the bases cytosine (C), thymine (T), and uracil (U) are pyrimidines, which contain a single ring (see Figure 2-17). Three of these bases—A, G, and C—are found in both DNA and RNA; however, T is found only in DNA and U only in RNA. (Note that the single-letter abbreviations for these bases are also commonly used to denote the entire nucleotides in nucleic acid polymers.)

A single nucleic acid strand has a backbone composed of repeating pentose-phosphate units from which the purine and pyrimidine bases extend as side groups. Like a polypeptide, a nucleic acid strand has an end-to-end chemical orientation: the 5end has a hydroxyl or phosphate group on the 5′ carbon of its terminal sugar; the 3end usually has a hydroxyl group on the 3′ carbon of its terminal sugar (Figure 5-2). This directionality, plus the fact that synthesis proceeds 5′ to 3′, has given rise to the convention that polynucleotide sequences are written and read in the 5′→3′ direction (from left to right); for example, the sequence AUG is assumed to be (5′)AUG(3′). As we will see, the 5′→3′ directionality of a nucleic acid strand is an important property of the molecule. The chemical linkage between adjacent nucleotides, commonly called a phosphodiester bond, actually consists of two phosphoester bonds, one on the 5′ side of the phosphate and another on the 3′ side.

image
FIGURE 5-2 Chemical directionality of a nucleic acid strand. Shown here are alternative representations of a single strand of DNA containing only three bases: cytosine (C), adenine (A), and guanine (G). (a) The chemical structure shows a hydroxyl group at the 3′ end and a phosphate group at the 5′ end. Note also that two phosphoester bonds link adjacent nucleotides; this two-bond linkage is commonly referred to as a phosphodiester bond. (b) In the “stick” diagram (top), the sugars are indicated as vertical lines and the phosphodiester bonds as slanting lines; the bases are denoted by their single-letter abbreviations. In the simplest representation (bottom), only the bases are indicated. By convention, a polynucleotide sequence is always written in the 5′→3′ direction (left to right) unless otherwise indicated.

The linear sequence of nucleotides linked by phosphodiester bonds constitutes the primary structure of a nucleic acid molecule. Like polypeptides, polynucleotides can twist and fold into three-dimensional conformations stabilized by noncovalent bonds. Although the primary structures of DNA and RNA are generally similar, their three-dimensional conformations are quite different. These structural differences are critical to the different functions of the two types of nucleic acids.