5 DNA Structure and Function

In the 1950s, Francis Crick and James Watson worked together at the University of Cambridge, England, to determine the structure of DNA. Other scientists, such as Linus Pauling and Maurice Wilkins, were also actively exploring this field. Pauling had discovered the secondary structure of proteins using X-ray crystallography. X-ray crystallography is a method for investigating molecular structure by observing the patterns formed by X-rays shot through a crystal of the substance. The patterns give important information about the structure of the molecule of interest. In Wilkins’ lab, researcher Rosalind Franklin was using X-ray crystallography to understand the structure of DNA. Watson and Crick were able to piece together the puzzle of the DNA molecule using Franklin’s data (Figure 1). Watson and Crick also had key pieces of information available from other researchers such as Chargaff’s rules. Chargaff had shown that of the four kinds of monomers (nucleotides) present in a DNA molecule, two types were always present in equal amounts and the remaining two types were also always present in equal amounts. This meant they were always paired in some way. In 1962, James Watson, Francis Crick, and Maurice Wilkins were awarded the Nobel Prize in Medicine for their work in determining the structure of DNA. Rosalind Franklin passed away from cancer in 1958 and was not recognized by the Nobel Committee, despite her research providing principle evidence toward our understanding of DNA (you can learn more about Rosalind Franklin here and here).

Now let’s consider the structure of the two types of nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). The building blocks of DNA are nucleotides, which are made up of three parts: a deoxyribose (5-carbon sugar), a phosphate group, and a nitrogenous base (Figure 2). There are four types of nitrogenous bases in DNA. Adenine (A) and guanine (G) are double-ringed purines, and cytosine (C) and thymine (T) are smaller, single-ringed pyrimidines. The nucleotide is named according to the nitrogenous base it contains.

The phosphate group of one nucleotide bonds covalently with the sugar molecule of the next nucleotide, and so on, forming a long polymer of nucleotide monomers. The sugar–phosphate groups line up in a “backbone” for each single strand of DNA, and the nucleotide bases stick out from this backbone. The carbon atoms of the five-carbon sugar are numbered clockwise from the oxygen as 1′, 2′, 3′, 4′, and 5′ (1′ is read as “one prime”). The phosphate group is attached to the 5′ carbon of one nucleotide and the 3′ carbon of the next nucleotide. In its natural state, each DNA molecule is actually composed of two single strands held together along their length with hydrogen bonds between the bases.

Watson and Crick proposed that the DNA is made up of two strands that are twisted around each other to form a right-handed helix, called a double helix. Base-pairing takes place between a purine and pyrimidine: namely, A pairs with T, and G pairs with C. In other words, adenine and thymine are complementary base pairs, and cytosine and guanine are also complementary base pairs. This is the basis for Chargaff’s rule; because of their complementarity, there is as much adenine as thymine in a DNA molecule and as much guanine as cytosine. Adenine and thymine are connected by two hydrogen bonds, and cytosine and guanine are connected by three hydrogen bonds. The two strands are anti-parallel in nature; that is, one strand will have the 3′ carbon of the sugar in the “upward” position, whereas the other strand will have the 5′ carbon in the upward position. The diameter of the DNA double helix is uniform throughout because a purine (two rings) always pairs with a pyrimidine (one ring) and their combined lengths are always equal. (Figure 3).

The Structure of RNA

There is a second nucleic acid in all cells called ribonucleic acid, or RNA. Like DNA, RNA is a polymer of nucleotides. Each of the nucleotides in RNA is made up of a nitrogenous base, a five-carbon sugar, and a phosphate group. In the case of RNA, the five-carbon sugar is ribose, not deoxyribose. Ribose has a hydroxyl group at the 2′ carbon, unlike deoxyribose, which has only a hydrogen atom (Figure 4).

RNA nucleotides contain the nitrogenous bases adenine, cytosine, and guanine. However, they do not contain thymine, which is instead replaced by uracil, symbolized by a “U.” RNA exists as a single-stranded molecule rather than a double-stranded helix. Molecular biologists have named several kinds of RNA on the basis of their function. These include messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA)—molecules that are involved in the production of proteins from the DNA code.

How DNA Is Arranged in the Cell

DNA is a working molecule; it must be replicated when a cell is ready to divide, and it must be “read” to produce the molecules, such as proteins, to carry out the functions of the cell. For this reason, the DNA is protected and packaged in very specific ways. In addition, DNA molecules can be very long. Stretched end-to-end, the DNA molecules in a single human cell would come to a length of about 2 meters. Thus, the DNA for a cell must be packaged in a very ordered way to fit and function within a structure (the cell) that is not visible to the naked eye. The chromosomes of prokaryotes are much simpler than those of eukaryotes in many of their features (Figure 5). Most prokaryotes contain a single, circular chromosome that is found in an area in the cytoplasm called the nucleoid.

The size of the genome in one of the most well-studied prokaryotes, Escherichia coli, is 4.6 million base pairs, which would extend a distance of about 1.6 mm if stretched out. So how does this fit inside a small bacterial cell? The DNA is twisted beyond the double helix in what is known as supercoiling. Some proteins are known to be involved in the supercoiling; other proteins and enzymes help in maintaining the supercoiled structure.

Eukaryotes, whose chromosomes each consist of a linear DNA molecule, employ a different type of packing strategy to fit their DNA inside the nucleus (Figure 6). At the most basic level, DNA is wrapped around proteins known as histones to form structures called nucleosomes. The DNA is wrapped tightly around the histone core. This nucleosome is linked to the next one by a short strand of DNA that is free of histones. This is also known as the “beads on a string” structure; the nucleosomes are the “beads” and the short lengths of DNA between them are the “string.” The nucleosomes, with their DNA coiled around them, stack compactly onto each other to form a 30-nm–wide fiber. This fiber is further coiled into a thicker and more compact structure. At the metaphase stage of mitosis, when the chromosomes are lined up in the center of the cell, the chromosomes are at their most compacted. They are approximately 700 nm in width, and are found in association with scaffold proteins.

In interphase, the phase of the cell cycle between mitoses at which the chromosomes are decondensed, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. There is a tightly packaged region that stains darkly, and a less dense region. The darkly staining regions usually contain genes that are not active, and are found in the regions of the centromere and telomeres. The lightly staining regions usually contain genes that are active, with DNA packaged around nucleosomes but not further compacted.

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