Chapter 2 – Orientation for the Bio-Curious  33

The nucleotide subunits can link to each other in two places, defined by the numbered

positions of the carbon atoms in the structure, in either the 3′ or the 5′ position (Figure 2.3d),

via a nucleosidic bond, again involving the loss of a molecule of water, which still permit

further linking of additional nucleotides from both the end 3′ and 5′ positions that were not

utilized in internucleotide binding, which can thus be subsequently repeated for adding more

subunits. In this way, a chain consisting of a potentially very long sequence of nucleotides

can be generated; natural DNA molecules in live cells can have a contour length of several

microns.

DNA strands have an ability to stably bind via base pair interactions (also known as

Watson–​Crick base pairing) to another complementary strand of DNA. Here, the indi­

vidual nucleotides can form stable multiple hydrogen bonds to nucleotides in the com­

plementary strand due to the tessellating nature of either the C–​G (three internucleotide

H-​bonds) or A–​T (two internucleotide H-​bonds) structures, generating a double-​helical

structure such that the H-​bonds of the base pairs span the axial core of the double helix,

while the negatively charged phosphate groups protrude away from the axis on the outside

of the double helix, thus providing additional stability through minimization of electro­

static repulsion.

This base pairing is utilized in DNA replication and in reading out of the genetic code

stored in the DNA molecule to make proteins. In DNA replication, errors can occur spon­

taneously from base pairing mismatch for which noncomplementary nucleotide bases are

paired, but there are error-​checking machines that can detect a substantial proposal of

these errors during replication and correct them. Single-​stranded DNA can exist, but in

the living cell, this is normally a transient state that is either stabilized by the binding of

specific proteins or will rapidly base pair with a strand having a complementary nucleotide

sequence.

Other interactions can occur above and below the planes of the nucleotide bases due

to the overlap of delocalized electron orbitals from the nucleotide rings, called “stacking

interactions,” which may result in heterogeneity in the DNA helical structures that are

dependent upon both the nucleotide sequence and the local physical chemistry environment,

which may result in different likelihood values for specific DNA structures than the base

pairing interactions along might suggest. For the majority of time under normal conditions

inside the cell, DNA will adopt a right-​handed helical conformation (if the thumb of your

right hand was aligned with the helix axis and your relaxed, index finger of that hand would

follow the grooves of the helix as they rotate around the axis) called “B-​DNA” (Figure 2.3d),

whose helical width is 2.0 nm and helical pitch is 3.4 nm consisting of a mean of 10.5 base

pair turns. Other stable helical conformations exist including A-​DNA, which has a smaller

helical pitch and wider width than B-​DNA, as well as Z-​DNA, which is a stable left-​handed

double helix. In addition, more complex structures can form through base pairing of mul­

tiple strands, including triple-​helix structures and Holliday junctions in which four indi­

vidual strands may be involved.

The importance of the phosphate backbone of DNA, that is, the helical lines of phos­

phate groups that protrude away from the central DNA helix to the outside, should not be

underestimated, however. A close inspection of native DNA phosphate backbones indicate

that this repeating negative charge is not only used by certain enzymes to recognize spe­

cific parts of DNA to bind to but perhaps more importantly is essential for the structural

stability of the double helix. For example, replacing the phosphate groups chemically using

noncharged groups results in significant structural instability for any DNA segment longer

than 100 nucleotide base pairs. Therefore, although the Watson–​Crick base pair model

includes no role for the phosphate background in DNA, it is just as essential.

KEY POINT 2.9

Although DNA can adopt stable double-​helical structures by virtue of base pairing,

several different double-​helical structures exist, and DNA may also adopt more com­

plex nonhelical structures.