Learning Objectives Describe the two types of nucleic acids and the function of each type. Describe the secondary structure of DNA and the importance of complementary base pairing. Describe how a new copy of DNA is synthesized. The repeating, or monomer, units that are linked together to form nucleic acids are known as nucleotides. The deoxyribonucleic acid (DNA) of a typical mammalian cell contains about 3 × 10 9 nucleotides. Nucleotides can be further broken down to phosphoric acid (H 3 PO 4 ), a pentose sugar (a sugar with five carbon atoms), and a nitrogenous base (a base containing nitrogen atoms). \[\mathrm{nucleic\: acids \underset{down\: into}{\xrightarrow{can\: be\: broken}} nucleotides \underset{down\: into}{\xrightarrow{can\: be\: broken}} H_3PO_4 + nitrogen\: base + pentose\: sugar} \nonumber \] If the pentose sugar is ribose, the nucleotide is more specifically referred to as a ribonucleotide , and the resulting nucleic acid is ribonucleic acid (RNA). If the sugar is 2-deoxyribose, the nucleotide is a deoxyribonucleotide , and the nucleic acid is DNA. The nitrogenous bases found in nucleotides are classified as pyrimidines or purines. Pyrimidines are heterocyclic amines with two nitrogen atoms in a six-member ring and include uracil, thymine, and cytosine. Purines are heterocyclic amines consisting of a pyrimidine ring fused to a five-member ring with two nitrogen atoms. Adenine and guanine are the major purines found in nucleic acids (Figure \(\PageIndex{1}\)). The formation of a bond between C1′ of the pentose sugar and N1 of the pyrimidine base or N9 of the purine base joins the pentose sugar to the nitrogenous base. In the formation of this bond, a molecule of water is removed. Table \(\PageIndex{1}\) summarizes the similarities and differences in the composition of nucleotides in DNA and RNA. The numbering convention is that primed numbers designate the atoms of the pentose ring, and unprimed numbers designate the atoms of the purine or pyrimidine ring. Composition DNA RNA purine bases adenine and guanine adenine and guanine pyrimidine bases cytosine and thymine cytosine and uracil pentose sugar 2-deoxyribose ribose inorganic acid phosphoric acid (H3PO4) H3PO4 The names and structures of the major ribonucleotides and one of the deoxyribonucleotides are given in Figure \(\PageIndex{2}\). Apart from being the monomer units of DNA and RNA, the nucleotides and some of their derivatives have other functions as well. Adenosine diphosphate (ADP) and adenosine triphosphate (ATP), shown in Figure \(\PageIndex{3}\), have a role in cell metabolism. Moreover, a number of coenzymes, including flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD + ), and coenzyme A, contain adenine nucleotides as structural components. Nucleic acids are large polymers formed by linking nucleotides together and are found in every cell. Deoxyribonucleic acid (DNA) is the nucleic acid that stores genetic information. If all the DNA in a typical mammalian cell were stretched out end to end, it would extend more than 2 m. Ribonucleic acid (RNA) is the nucleic acid responsible for using the genetic information encoded in DNA to produce the thousands of proteins found in living organisms. Primary Structure of Nucleic Acids Nucleotides are joined together through the phosphate group of one nucleotide connecting in an ester linkage to the OH group on the third carbon atom of the sugar unit of a second nucleotide. This unit joins to a third nucleotide, and the process is repeated to produce a long nucleic acid chain (Figure \(\PageIndex{4}\)). The backbone of the chain consists of alternating phosphate and sugar units (2-deoxyribose in DNA and ribose in RNA). The purine and pyrimidine bases branch off this backbone. Each phosphate group has one acidic hydrogen atom that is ionized at physiological pH. This is why these compounds are known as nucleic acids. Like proteins, nucleic acids have a primary structure that is defined as the sequence of their nucleotides. Unlike proteins, which have 20 different kinds of amino acids, there are only 4 different kinds of nucleotides in nucleic acids. For amino acid sequences in proteins, the convention is to write the amino acids in order starting with the N-terminal amino acid. In writing nucleotide sequences for nucleic acids, the convention is to write the nucleotides (usually using the one-letter abbreviations for the bases, shown in Figure \(\PageIndex{4}\)) starting with the nucleotide having a free phosphate group, which is known as the 5′ end, and indicate the nucleotides in order. For DNA, a lowercase d is often written in front of the sequence to indicate that the monomers are deoxyribonucleotides. The final nucleotide has a free OH group on the 3′ carbon atom and is called the 3′ end . The sequence of nucleotides in the DNA segment shown in Figure \(\PageIndex{4}\) would be written 5′-dG-dT-dA-dC-3′, which is often further abbreviated to dGTAC or just GTAC. Secondary Structure of DNA The three-dimensional structure of DNA was the subject of an intensive research effort in the late 1940s to early 1950s. Initial work revealed that the polymer had a regular repeating structure. In 1950, Erwin Chargaff of Columbia University showed that the molar amount of adenine (A) in DNA was always equal to that of thymine (T). Similarly, he showed that the molar amount of guanine (G) was the same as that of cytosine (C). Chargaff drew no conclusions from his work, but others soon did. At Cambridge University in 1953, James D. Watson and Francis Crick announced that they had a model for the secondary structure of DNA. Using the information from Chargaff’s experiments (as well as other experiments) and data from the X ray studies of Rosalind Franklin (which involved sophisticated chemistry, physics, and mathematics), Watson and Crick worked with models that were not unlike a child’s construction set and finally concluded that DNA is composed of two nucleic acid chains running antiparallel to one another—that is, side-by-side with the 5′ end of one chain next to the 3′ end of the other. Moreover, as their model showed, the two chains are twisted to form a double helix—a structure that can be compared to a spiral staircase, with the phosphate and sugar groups (the backbone of the nucleic acid polymer) representing the outside edges of the staircase. The purine and pyrimidine bases face the inside of the helix, with guanine always opposite cytosine and adenine always opposite thymine. These specific base pairs, referred to as complementary bases, are the steps, or treads, in our staircase analogy (Figure \(\PageIndex{5}\)). The structure proposed by Watson and Crick provided clues to the mechanisms by which cells are able to divide into two identical, functioning daughter cells; how genetic data are passed to new generations; and even how proteins are built to required specifications. All these abilities depend on the pairing of complementary bases. Figure \(\PageIndex{6}\) shows the two sets of base pairs and illustrates two things. First, a pyrimidine is paired with a purine in each case, so that the long dimensions of both pairs are identical (1.08 nm). If two pyrimidines were paired or two purines were paired, the two pyrimidines would take up less space than a purine and a pyrimidine, and the two purines would take up more space, as illustrated in Figure \(\PageIndex{7}\). If these pairings were ever to occur, the structure of DNA would be like a staircase made with stairs of different widths. For the two strands of the double helix to fit neatly, a pyrimidine must always be paired with a purine. The second thing you should notice in Figure \(\PageIndex{6}\) is that the correct pairing enables formation of three instances of hydrogen bonding between guanine and cytosine and two between adenine and thymine. The additive contribution of this hydrogen bonding imparts great stability to the DNA double helix. We previously stated that deoxyribonucleic acid (DNA) stores genetic information, while ribonucleic acid (RNA) is responsible for transmitting or expressing genetic information by directing the synthesis of thousands of proteins found in living organisms. But how do the nucleic acids perform these functions? Three processes are required: (1) replication , in which new copies of DNA are made; (2) transcription , in which a segment of DNA is used to produce RNA; and (3) translation , in which the information in RNA is translated into a protein sequence. DNA: Self-Replication New cells are continuously forming in the body through the process of cell division. For this to happen, the DNA in a dividing cell must be copied in a process known as replication. The complementary base pairing of the double helix provides a ready model for how genetic replication occurs. If the two chains of the double helix are pulled apart, disrupting the hydrogen bonding between base pairs, each chain can act as a template , or pattern, for the synthesis of a new complementary DNA chain. The nucleus contains all the necessary enzymes, proteins, and nucleotides required for this synthesis. A short segment of DNA is “unzipped,” so that the two strands in the segment are separated to serve as templates for new DNA. DNA polymerase, an enzyme, recognizes each base in a template strand and matches it to the complementary base in a free nucleotide. The enzyme then catalyzes the formation of an ester bond between the 5′ phosphate group of the nucleotide and the 3′ OH end of the new, growing DNA chain. In this way, each strand of the original DNA molecule is used to produce a duplicate of its former partner (Figure \(\PageIndex{8}\)). Whatever information was encoded in the original DNA double helix is now contained in each replicate helix. When the cell divides, each daughter cell gets one of these replicates and thus all of the information that was originally possessed by the parent cell. Example \(\PageIndex{1}\) A segment of one strand from a DNA molecule has the sequence 5′‑TCCATGAGTTGA‑3′. What is the sequence of nucleotides in the opposite, or complementary, DNA chain? Solution Knowing that the two strands are antiparallel and that T base pairs with A, while C base pairs with G, the sequence of the complementary strand will be 3′‑AGGTACTCAACT‑5′. Exercise \(\PageIndex{1}\) A segment of one strand from a DNA molecule has the sequence 5′‑CCAGTGAATTGCCTAT‑3′. What is the sequence of nucleotides in the opposite, or complementary, DNA chain? Answer 3′‑GGTCACTTAACGGATA‑5′. Summary Nucleotides are composed of phosphoric acid, a pentose sugar (ribose or deoxyribose), and a nitrogen-containing base (adenine, cytosine, guanine, thymine, or uracil). Ribonucleotides contain ribose, while deoxyribonucleotides contain deoxyribose. DNA is the nucleic acid that stores genetic information. RNA is the nucleic acid responsible for using the genetic information in DNA to produce proteins. Nucleic acid sequences are written starting with the nucleotide having a free phosphate group (the 5′ end). Two DNA strands link together in an antiparallel direction and are twisted to form a double helix. The nitrogenous bases face the inside of the helix. Guanine is always opposite cytosine, and adenine is always opposite thymine. In DNA replication, each strand of the original DNA serves as a template for the synthesis of a complementary strand. DNA polymerase is the primary enzyme needed for replication.