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2-3 Nucleic acids store information and process it
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[Prev] | [Next]- DNA and RNA are composed of two parts, the sugar phosphate backbone and nucleotide bases.
- The bases in DNA are purines (adenine and guanine) and pyrimidines (cytosine and thymine). RNA contains the same bases, except uracil is substituted for thymine and they contain an extra 5'-hydroxyl.
- DNA polymers can be thousands of base pairs long. RNA polymers are hundreds to thousands of bases long.
- RNA is single-stranded. DNA is double-stranded and forms a double helix in the cell.
- RNA molecules have significant secondary and tertiary structure that is important in their functions.
Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are involved in information storage and processing. DNA serves as the cell's hereditary information, while RNA is involved in converting that information into functional products, such as proteins. RNA and DNA are long polymers of only 4 nucleotides: adenine, guanine, cytosine and thymine (or uracil for RNA). Figure 2-4 lists the structure of the five nucleotides found in nucleic acids.
Figure 2-4 The structure of nucleotides.
The nucleotides for adenosine (A), guanine (G), cytosine (C ) and thymine (T) as found in DNA are shown. The first three are also found in RNA, but when incorporated into that polymer, the associated sugar has two hydroxyls, as shown in the model of uracil (U). Uracil is the RNA equivalent of the DNA nucleotide thymine.
The nucleotide structure can be broken down into two parts: the sugar-phosphate backbone and the base. All nucleotides share the sugar-phosphate backbone, while the base distinguishes each type of nucleotide. Linking these monomer units together using a 5’-oxygen on the phosphate and the 3’-hydroxyl group on the sugar forms the nucleotide polymer as shown in Figure 2-5. Many thousands of DNA nucleotides are strung together to form genes and chromosomes.
Figure 2-5 A schematic of the nucleic acid polymer
In this picture the bases of the two anti-parallel (running in opposite direction) strands of a DNA double helix are shown. Note the sugar-phosphate backbone from which the bases extend and pair with matching bases from the other strand. The dashed lines show hydrogen bonds between the base pairs.
The bases of the four nucleotides are different, but there is also a pattern. Adenine (A) and guanine (G) are purines, and therefore have a distinctive two-ring structure; they differ in the chemical groups attached to the rings. Likewise, cytosine (C), thymine (T) and uracil (U) are all pyrimidines and share a single-ringed structure, but also differ in their attached groups. Not surprisingly, as these extra chemical groups distinguish the different purines and pyrimidines structurally, they are also responsible for their important functional differences as well.
The bases in a nucleic acid polymer are capable of forming hydrogen bonds with neighboring bases on a second strand of nucleic acid, a process termed base pairing. However, there are rules to this association. Adenine is capable of forming two hydrogen bonds with thymine (or uracil) and cytosine can base pair with guanine, forming three hydrogen bonds. Some of these bonds require the extra chemical groups mentioned above. If two single strands of nucleic acid have sequences that can base pair along the polymer (such sequences are sometimes said to complement), they will generate a long double-stranded polymer that has a staircase topology as shown in Figure 2-6. This structure is termed a double helix, since two strands form the molecule and it spirals around an axis in a regular pattern. Such a reaction between two complementary DNA strands is spontaneous: if you mix two complementary single strands of nucleic acid together in a test tube at a reasonable temperature, pH and salt concentration, they will find each other and anneal to form a double-stranded polymer.
Figure 2-6 The Double Helix
Note how the two nucleic acid strands spiral around each other in a regular repeating pattern. There are 10 bases per turn of the double helix. Bases pair with one another in the center of the helix cylinder and form what some have likened to a spiral staircase. The above figure can be rotated by clicking on the arrows.
Secondary and Tertiary DNA Structures
DNA almost always exists in cells as a double-stranded structure of complementing strands. It happens that this double-stranded form is rather stable, and resists tight twists and turns. It is often assumed that the stability is due to the hydrogen bonding between the bases, but this is not the case (the bases would hydrogen bond just as well to water). Instead, it is largely due to the interaction between adjacent base pairs along the helix, which is termed "base stacking" Figure 2-7 for an example. Finally, the larger organization of the DNA strands with respect to each other, termed the tertiary structure, is also fairly similar in all DNA molecules. One implication is that proteins that want to distinguish between different DNA molecules must do so by reading different primary structure sequences by interacting with the outer surface of the base pairs.
Figure 2-7 A molecular model of the lac repressor
The repressor binding to its recognition sequence. Any DNA-binding protein that recognize specific DNA sequences must make specific contacts with that recognition sequence by reading the pattern of bases in the DNA. These proteins do this by making very specific contacts between themselves and those atoms on DNA that are different in the different bases. In this figure, the DNA helix is shown by the ball-and-stick figure running along the bottom and the protein is depicted by cylinders (which refer to alpha helices) and other "squiggles" (which refer to any other structure in the protein). The point of the figure are that the DNA is not opened up and that the recognition regions of the proteins are very often alpha helices that lay parallel with or perpendicular to the DNA helix. Not shown are the side chains of the amino acids that actual make the specific contacts with the DNA. In this and subsequent molecular figures, of three different displays will be shown: ball and stick, which shows all atoms larger than hydrogen; ribbon models, in which a ribbon that runs along the carbon backbone of the protein is displayed; and space-filling models, where the actual atomic surface of the molecule is shown. Sometimes, as in this figure, the ribbon form is modified slightly be showing cylinders for alpha helices instead of an actual helix as in Fig. 2-11. Most of the structures shown in this text are the product of X-ray crystallography, which essentially displays the position of every atom (larger than hydrogen) in a molecule. Increasingly all biological questions are being thought about in terms of these structures at the atomic scale.
Structures of RNA
In composition and therefore primary structure, RNA is similar to DNA, except that uracil (U) takes the place of thymine in the molecule and the ribose unit on each sugar contains a additional hydroxyl group. However, most RNA in cells exists as single-stranded molecules and not a complex of two different strands as with DNA. Now if complementary base sequences are present in an RNA molecule, it can fold back upon itself and base pair, so that many RNA molecules have at least some double-stranded regions. However, this bending and folding means that RNA molecules typically have much more complicated tertiary structures than does DNA. Both the single-stranded loops and the double-stranded stems are critical for the function of most RNA molecules. Many are involved in creating physical structures, such as ribosomes, that are involved in processing information. The other general class of RNAs are messenger RNAs, which represent a version of the DNA primary structure that is suitable for translation into protein.
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