The secondary structure of DNA refers to its three-dimensional configuration—its fundamental helical structure. DNA’s secondary structure can assume a variety of configurations, depending on its base sequence and the conditions in which it is placed.

THE DOUBLE HELIX A fundamental characteristic of DNA’s secondary structure is that it consists of two polynucleotide strands wound around each other: it’s a double helix. The sugar–phosphate linkages are on the outside of the helix, and the bases are stacked in the interior of the molecule (see Figure 8.11). The two polynucleotide strands run in opposite directions: they are antiparallel, which means that the 5′ end of one strand is opposite the 3′ end of the other strand.

The strands are held together by two types of molecular forces. Hydrogen bonds link the bases on opposite strands (see Figure 8.11). These bonds are relatively weak compared with the covalent phosphodiester bonds that connect the sugar and phosphate groups of adjoining nucleotides on the same strand. As we will see, several important functions of DNA require the separation of its two nucleotide strands, and this separation can be readily accomplished because of the relative ease of breaking and reestablishing the hydrogen bonds.

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The nature of the hydrogen bond imposes a limitation on the types of bases that can pair. Adenine normally pairs only with thymine through two hydrogen bonds, and cytosine normally pairs only with guanine through three hydrogen bonds (see Figure 8.11). Because three hydrogen bonds form between C and G and only two hydrogen bonds form between A and T, C–G pairing is stronger than A–T pairing. The specificity of the base pairing means that wherever there is an A on one strand, there must be a T in the corresponding position on the other strand, and wherever there is a G on one strand, a C must be on the other. The two polynucleotide strands of a DNA molecule are therefore not identical, but rather complementary DNA strands. The complementary nature of the two nucleotide strands provides for efficient and accurate DNA replication (as we will see in Chapter 9).

The second force that holds the two DNA strands together is the interaction between the stacked base pairs in the interior of the molecule. Stacking means that adjacent bases are aligned so that their rings are parallel and stack on top of one another. The stacking interactions stabilize the DNA molecule but do not require that any particular base follow another. Thus, the base sequence of the DNA molecule is free to vary, allowing DNA to carry genetic information. TRY PROBLEMS 25 AND 27

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DIFFERENT SECONDARY STRUCTURES As we have seen, DNA normally consists of two polynucleotide strands that are antiparallel and complementary (exceptions are the single-stranded DNA molecules found in a few viruses). The precise three-dimensional shape of the molecule can vary, however, depending on the conditions in which the DNA is placed and, in some cases, on the base sequence itself.

The three-dimensional structure of DNA described by Watson and Crick is termed the B-DNA structure (Figure 8.12). This structure exists when plenty of water surrounds the molecule and there are no unusual base sequences in the DNA—conditions that are likely to be present in cells. The B-DNA structure is the most stable configuration for a random sequence of nucleotides under physiological conditions, and most evidence suggests that it is the predominant structure in the cell.

B-DNA is a right-handed helix, meaning that it has a clockwise spiral. There are approximately 10 base pairs (bp) per 360-degree rotation of the helix, so each base pair is twisted 36 degrees relative to the adjacent bases (Figure 8.12b). The base pairs are 0.34 nanometer (nm) apart; so each complete rotation of the molecule encompasses 3.4 nm. The diameter of the helix is 2 nm, and the bases are perpendicular to the long axis of the DNA molecule. A space-filling model shows that B-DNA has a slim and elongated structure (Figure 8.12a). The spiraling of the nucleotide strands creates major and minor grooves in the helix, features that are important for the binding of some proteins that regulate the expression of genetic information (see Chapter 12).

Another secondary structure that DNA can assume is the A-DNA structure, which exists if less water is present. Like B-DNA, A-DNA is a right-handed helix (Figure 8.13a), but it is shorter and wider than B-DNA (Figure 8.13b) and its bases are tilted away from the main axis of the molecule. A-DNA has been detected in some DNA–protein complexes and in spores of some bacteria.

A radically different secondary structure, called Z-DNA (Figure 8.13c), forms a left-handed helix. In this structure, the sugar–phosphate backbone zigzags back and forth, giving rise to its name. A Z-DNA structure can result if the molecule contains particular base sequences, such as stretches of alternating C and G nucleotides. Researchers have found that Z-DNA-specific antibodies bind to regions of the DNA that are being transcribed into RNA, suggesting that Z-DNA may play some role in gene expression. Other secondary structures of DNA also exist, such as H-DNA, in which one part of the DNA unwinds and a single-stranded nucleotide chain then pairs with the two strands of another region to form a three-stranded helix.

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