"Nucleic acids"

Date:
1957
Reference:
PP/CRI/H/2/21
Catalogue details

Licence: In copyright

Credit: "Nucleic acids". Source: Wellcome Collection.

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    NUCLEIC ACIDS These polymers appear to carry the pattern of living matter from one generation to the next. Their basic chain consists of sugars joined by phosphates. Attached to the sugars, in turn, are bases by F. H. C. Crick If proteins are the principal stuff of life, the nucleic acids are its blue prints—the molecules on which the Secret of Life, if we may speak of such a thing, is written. The nucleic acids oc cur in every living cell. It seems, accord ing to our best present information, that they direct the manufacture of proteins and hold the key to the hereditary con stitution of all living things. Like the proteins, the nucleic acids are high poly mers, but they are polymers with a dif ference. If we ever achieve a complete understanding of their construction and behavior, we shall probably have the answer to how nature goes about form ing each living organism. In this article I shall give my own view of the meaning of the facts learned about the nucleic acids so far. A great deal of work has been done on these sub stances, and there is considerable room for disagreement in interpreting the find ings. But it is possible to form a general theory which seems to fit most of the known facts and serves as an attractive working hypothesis. There are two kinds of nucleic acid: DNA, short for deoxyribonucleic acid, and RNA, ribonucleic acid. DNA is al ways found in the nucleus of the cell, RNA mainly in the cytoplasm outside the nucleus. Chemically they are very similar. Each consists of a long chain of phosphate and sugar molecules with small side groups (called bases) at tached to the sugars [ see diagrams on pages 190 and 191 ]. In DNA the sugar is deoxyribose; in RNA it is a very slightly different molecule called ribose. The two also differ in one of the four bases at tached as side groups. Both contain ade nine, guanine and cytosine, but in the case of DNA the fourth base is thymine, whereas in RNA it is uracil. The bases along the backbone of the nucleic acid do not follow a regular or der (such as ABCDABCD and so on). We have some reason to believe that the sequence in each case has a particular meaning and determines the function of the molecule, just as the sequence of let ters in this sentence conveys my mean ing to you as you read. But more about this later. Electron-microscope pictures show that pieces of DNA are long and rather stiff, like a piece of cord. And by X-ray analysis it has been found that DNA is actually a double molecule, with one chain twined around the other in helical fashion. The bases of one chain fit neatly onto the bases of the other. But in order to fit, a given base on one chain must be opposite a particular one on the other: guanine pairs only with cytosine and adenine only with thymine. Thus the se quence of bases on one chain determines the sequence on the other. TVTuch less is known about the struc- ture of RNA, but some progress has been made in creating simpler syn thetic analogues. One of these polymers has only the base adenine attached to the backbone, and is known as polyadenylic acid—or Poly A to its friends. Under cer tain circumstances Poly A probably takes the form of two chains wound around each other, with the adenine of one chain fitting onto the adenine of the other. Another synthetic analogue to RNA has been made with uracil as the base—it is known as Poly U. When Poly U and Poly A are put together in a solu tion, a remarkable combination takes place: the two chains join in an inter twined helical structure like that of DNA. It seems very likely that the struc ture is held together mainly by hydrogen bonds between the adenines on one chain and the uracils on the other. Alex ander Rich and his colleagues at the Na tional Institutes of Health in Bethesda, Md., who deciphered this structure, have found that in the presence of magnesium the mixture of Poly A and Poly U seems to form a three-chain structure, one Poly A chain joining up with two Pòly U chains. The details of this new structure are eagerly awaited. Other interesting questions arise. Does Poly G (made with guanine) pair up with Poly C (contain ing cytosine), as the DNA pairing would lead us to expect? Unfortunately it seems very difficult to produce a good Poly G, so for the present we cannot answer this question. There are indications that natural RNA consists of two chains, but it gives rather poor X-ray pictures, suggesting an irregular structure. Whether the dis order is inherent in the molecule or is produced during the extraction of RNA from the cell we cannot say, because we have little information to tell us what RNA is like inside living cells. Perhaps in the cell it assumes an orderly and sig nificant configuration only when it is combined with DNA or protein. Some progress has recently been made toward synthesizing the nucleic acids with the help of enzymes extracted from living cells. Marianne Grunberg-Manago and Severo Ochoa at New York Univer sity discovered an enzyme system in cer tain bacteria with which they were able to make RNA-like molecules, as well as Poly A and Poly U. Arthur Kornberg and his colleagues at Washington Uni versity in St. Louis found a different sys tem, also in bacteria, which produces DNA-like material. The RNA-type poly mers were made from diphosphates of the nucleotides corresponding to the four natural bases (adenine, uracil, guanine and cytosine). When all four diphosphates were provided at the same