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Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002.

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A DNA Molecule Consists of Two Complementary Chains of Nucleotides

ADNAmolecule consists of two long polynucleotide chains composed of four types ofnucleotide subunits. Each of these chains is known as aDNA chain, or aDNA strand.Hydrogen bonds between thebase portions of the nucleotides hold the two chains together (Figure 4-3). As we saw in Chapter 2 (Panel 2-6, pp. 120-121), nucleotides are composed of a five-carbonsugar to which are attached one or more phosphate groups and a nitrogen-containing base. In the case of the nucleotides in DNA, the sugar is deoxyribose attached to a single phosphate group (hence the namedeoxyribonucleic acid), and the base may be eitheradenine (A), cytosine (C), guanine (G), orthymine (T). The nucleotides are covalently linked together in a chain through the sugars and phosphates, which thus form a “backbone” of alternating sugar-phosphate-sugar-phosphate (seeFigure 4-3). Because only the base differs in each of the four types of subunits, each polynucleotide chain in DNA is analogous to a necklace (the backbone) strung with four types of beads (the four bases A, C, G, and T). These same symbols (A, C, G, and T) are also commonly used to denote the four different nucleotides—that is, the bases with their attached sugar and phosphate groups.

Figure 4-3

DNA and its building blocks. DNA is made of four types of nucleotides, which are linked covalently into a polynucleotide chain (a DNA strand) with a sugar-phosphate backbone from which the bases (A, C, G, and T) extend. A DNA molecule is composed of two(more...)

The way in which thenucleotide subunits are lined together gives aDNA strand a chemical polarity. If we think of eachsugar as a block with a protruding knob (the 5′ phosphate) on one side and a hole (the 3′hydroxyl) on the other (seeFigure 4-3), each completed chain, formed by interlocking knobs with holes, will have all of its subunits lined up in the same orientation. Moreover, the two ends of the chain will be easily distinguishable, as one has a hole (the 3′ hydroxyl) and the other a knob (the 5′ phosphate) at its terminus. This polarity in a DNA chain is indicated by referring to one end as the3′end and the other as the5′end.

The three-dimensional structure ofDNA—thedouble helix—arises from the chemical and structural features of its two polynucleotide chains. Because these two chains are held together by hydrogen bonding between the bases on the different strands, all the bases are on the inside of the double helix, and thesugar-phosphate backbones are on the outside (seeFigure 4-3). In each case, a bulkier two-ringbase (apurine; seePanel 2-6, pp. 120–121) is paired with a single-ring base (apyrimidine); A always pairs with T, andG with C (Figure 4-4). Thiscomplementary base-pairing enables thebase pairs to be packed in the energetically most favorable arrangement in the interior of the double helix. In this arrangement, eachbase pair is of similar width, thus holding the sugar-phosphate backbones an equal distance apart along the DNAmolecule. To maximize the efficiency of base-pair packing, the two sugar-phosphate backbones wind around each other to form a double helix, with one complete turn every ten base pairs (Figure 4-5).

Figure 4-4

Complementary base pairs in the DNA double helix. The shapes and chemical structure of the bases allow hydrogen bonds to form efficiently only between A and T and between G and C, where atoms that are able to form hydrogen bonds (see Panel 2-3, pp. 114–115)(more...)

Figure 4-5

The DNA double helix. (A) A space-filling model of 1.5 turns of the DNA double helix. Each turn of DNA is made up of 10.4 nucleotide pairs and the center-to-center distance between adjacent nucleotide pairs is 3.4 nm. The coiling of the two strands around(more...)

The members of eachbase pair can fit together within thedouble helix only if the two strands of the helix areantiparallel—that is, only if the polarity of one strand is oriented opposite to that of the other strand (seeFigures 4-3 and4-4). A consequence of these base-pairing requirements is that each strand of aDNAmolecule contains a sequence of nucleotides that is exactlycomplementary to thenucleotide sequence of its partner strand.

The Structure of DNA Provides a Mechanism for Heredity

Genes carry biological information that must be copied accurately for transmission to the next generation each time a cell divides to form two daughter cells. Two central biological questions arise from these requirements: how can the information for specifying an organism be carried in chemical form, and how is it accurately copied? The discovery of the structure of theDNAdouble helix was a landmark in twentieth-century biology because it immediately suggested answers to both questions, thereby resolving at the molecular level the problem of heredity. We discuss briefly the answers to these questions in thissection, and we shall examine them in more detail in subsequent chapters.

DNA encodes information through the order, or sequence, of the nucleotides along each strand. Eachbase—A, C, T, orG—can be considered as a letter in a four-letter alphabet that spells out biological messages in the chemical structure of the DNA. As we saw in Chapter 1, organisms differ from one another because their respective DNA molecules have differentnucleotide sequences and, consequently, carry different biological messages. But how is the nucleotide alphabet used to make messages, and what do they spell out?

As discussed above, it was known well before the structure ofDNA wasdetermined that genes contain the instructions for producing proteins. The DNA messages must therefore somehow encode proteins (Figure 4-6). This relationship immediately makes the problem easier to understand, because of the chemical character of proteins. As discussed in Chapter 3, the properties of aprotein, which are responsible for its biological function, are determined by its three-dimensional structure, and its structure is determined in turn by the linear sequence of the amino acids of which it is composed. The linear sequence of nucleotides in agene must therefore somehow spell out the linear sequence of amino acids in a protein. The exact correspondence between the four-letternucleotide alphabet of DNA and the twenty-letteramino acid alphabet of proteins—thegenetic code—is not obvious from the DNA structure, and it took over a decade after the discovery of thedouble helix before it was worked out. In Chapter 6 we describe this code in detail in the course of elaborating the process, known asgeneexpression, through which a cell translates the nucleotide sequence of a gene into the amino acid sequence of a protein.

Figure 4-6

The relationship between genetic information carried in DNA and proteins.

The complete set of information in an organism'sDNA is called itsgenome, and it carries the information for all the proteins the organism will ever synthesize. (The termgenome is also used to describe the DNA that carries this information.) The amount of information contained in genomes is staggering: for example, a typical human cell contains 2 meters of DNA. Written out in the four-letternucleotide alphabet, the nucleotide sequence of a very small humangene occupies a quarter of a page of text (Figure 4-7), while the complete sequence of nucleotides in the human genome would fill more than a thousand books the size of this one. In addition to other critical information, it carries the instructions for about 30,000 distinct proteins.

Figure 4-7

The nucleotide sequence of the human β-globin gene. This gene carries the information for the amino acid sequence of one of the two types of subunits of the hemoglobin molecule, which carries oxygen in the blood. A different gene, the α-globin(more...)

At eachcell division, the cell must copy itsgenome to pass it to both daughter cells. The discovery of the structure ofDNA also revealed the principle that makes this copying possible: because each strand of DNA contains a sequence of nucleotides that is exactlycomplementary to thenucleotide sequence of its partner strand, each strand can act as atemplate, or mold, for the synthesis of a new complementary strand. In other words, if we designate the two DNA strands as S and S′, strand S can serve as atemplate for making a new strand S′, while strand S′ can serve as a template for making a new strand S (Figure 4-8). Thus, the genetic information in DNA can be accurately copied by the beautifully simple process in which strand S separates from strand S′, and each separated strand then serves as a template for the production of a new complementary partner strand that is identical to its former partner.

Figure 4-8

DNA as a template for its own duplication. As the nucleotide A successfully pairs only with T, and G with C, each strand of DNA can specify the sequence of nucleotides in its complementary strand. In this way, double-helical DNA can be copied precisely.(more...)

The ability of each strand of aDNAmolecule to act as atemplate for producing acomplementary strand enables a cell to copy, orreplicate, its genes before passing them on to its descendants. In the next chapter we describe the elegant machinery the cell uses to perform this enormous task.

In Eucaryotes, DNA Is Enclosed in a Cell Nucleus

Nearly all theDNA in a eucaryotic cell is sequestered in anucleus, which occupies about 10% of the total cell volume. Thiscompartment is delimited by anuclear envelope formed by two concentriclipid bilayer membranes that are punctured at intervals by large nuclear pores, which transport molecules between the nucleus and thecytosol. The nuclear envelope is directly connected to the extensive membranes of theendoplasmic reticulum. It is mechanically supported by two networks of intermediate filaments: one, called thenuclear lamina, forms a thin sheetlike meshwork inside the nucleus, just beneath theinner nuclear membrane; the other surrounds theouter nuclear membrane and is less regularly organized (Figure 4-9).

Figure 4-9

A cross-sectional view of a typical cell nucleus. The nuclear envelope consists of two membranes, the outer one being continuous with the endoplasmic reticulum membrane (see also Figure 12-9). The space inside the endoplasmic reticulum (the ER lumen)(more...)

Thenuclear envelope allows the many proteins that act onDNA to be concentrated where they are needed in the cell, and, as we see in subsequent chapters, it also keeps nuclear and cytosolic enzymes separate, a feature that is crucial for the proper functioning of eucaryotic cells. Compartmentalization, of which thenucleus is an example, is an important principle of biology; it serves to establish an environment in which biochemical reactions are facilitated by the high concentration of both substrates and the enzymes that act on them.

Summary

Genetic information is carried in the linear sequence of nucleotides inDNA. Eachmolecule of DNA is adouble helix formed from twocomplementary strands of nucleotides held together by hydrogen bonds betweenG-C and A-Tbase pairs. Duplication of the genetic information occurs by the use of one DNA strand as atemplate for formation of a complementary strand. The genetic information stored in an organism's DNA contains the instructions for all the proteins the organism will ever synthesize. In eucaryotes, DNA is contained in the cellnucleus.