FIG. 7-5 Nucleotides are joined together by phos- phodiester bonds between the 3'-OH and 5'-P posi­tions. There is a free 5'-P at one end of the polynu­cleotide chain and a free 3'- OH at the other end.

Structure of dna 195

phate forms a bridge between the number 3-carbon of one deoxyribose sugar molecule and the number 5-carbon of another. At one end of the chain there is no phosphate bonded to the 3-carbon of a deoxyri­bose, and at the other end of the molecule, the phos­phate attached to the 5-carbon is not involved in forming a phosphodiester linkage. Thus there is a free hydroxyl group at the 3-carbon position at one end of the chain (3'-OH free end) and there is a free phosphate group at the 5-carbon position at the other end (5'-P free end). This imparts a second important property on the DNA macromolecule—that of direc­tionality.

Having different groups free at the different ends of the molecule distinguishes one end from the other (like left from right) thereby permitting the molecule to be read from a particular direction. This is espe­cially critical for a molecule whose purpose is to store and to transmit genetic information because it estab­

lishes the basis for the correct direction for reading the order of nucleotides that encode the genetic in­formation within the DNA macromolecule.

The chains of DNA macromolecules are different at

either end, which allows directional recognition.

DNA Double Helix—Complementarity

There are two chains of nucleotides in the DNA macromolecule. The two polynucleotide chains that comprise the DNA double helix run in opposite di­rections—one chain runs from the 3'-OH to the 5'-P free end and the complementary chain runs from the 5'-P to the 3'-OH free end. These complementary chains twist together to form an arrangement called a double helix (FIG. 7-6).

The two chains of the DNA double helix are held together by hydrogen bonding between complemen­tary chains. Two of the nitrogenous bases (C and T)

FIG. 7-6 The double helix is the fundamental structure of the DNA macromolecule. The two strands are held together by hydrogen bonding between complementary base pairs. There are three hydrogen bonds between the base pairs guanine and cytosine and two hy­drogen bonds between the base pairs adenine and thymine.

In the early 1950s, James Watson, who had only recently received a doctoral degree from Indiana University, teamed with Francis Crick, a Cambridge University re­searcher, and pieced together the available data to de­termine the chemical structure of the DNA molecule, showing how DNA could store and transmit hereditary information (see Figure).

Watson and Crick reasoned that the double-ringed adenine and guanine molecules were probably paired with the single-ringed thymine and cytosine molecules along the entire length of DNA. This would fit the ob­servation made by Erwin Chargaff in the United States in the late 1940s that in any given DNA macromolecule the amount of adenine present is always equal to the amount of thymine and the amount of cytosine is al­ways equal to the amount of guanine. It also was con­sistent with the observations of Maurice Wilkins and Rosalind Franklin at Cambridge University in England, who, using X-ray diffraction methods, showed that DNA was long and thin, with a uniform diameter. If this was not the case, then DNA would bulge where the two double rings were paired and narrow where two single rings were paired, something that was never seen in the X-ray diffraction images of Wilkins and Franklin.

The problem Watson and Crick had was that the structural formulas for the nucleic acid bases guanine and thymine that were in the organic chemistry books at that time were wrong. Because they were trying to build a model with the wrong structural representations for these molecules, they were unable to get the mole­cules to fit in a way that would be stabilized by hydro­gen bonding between their atoms. Only after getting the structural forms of guanine and thymine corrected dur­ing a chance meeting with a visiting scientist were Wat­son and Crick able to build the correct model of DNA. Once they had the accurate structures, they began shift­ing the bases in and out of various pairing possibilities.

They next used a plumb line and a measuring stick to determine the relative positions of all of the atoms in a single nucleotide. By assuming a helical shape like a spiral staircase, it became clear that the locations of the atoms in one nucleotide would automatically generate the position of the other. They had constructed a model of the DNA double helix. The model Watson and Crick constructed also showed how the chains could be sepa­rated and how each could code for a new complemen­tary chain, thereby unraveling the mystery of how a chemical could pass hereditary information to the next generation with such fidelity.

1. James Watson at age 23 and Francis Crick at age 34 developed a model for the structure of DNA while working at the Cavendish Laboratory at Cambridge University, England. The model explained how DNA can transmit hereditary information. They announced their discovery of the molecular structure of DNA in 1953 and shared the Nobel prize for medicine in 1962 along with Maurice Wilkins.

2. In 1993, on the fortieth anniversary of their discovery, they again posed with their model of DNA, which has proven to be correct.