In the final analysis, some explanation must be given for any interaction of metals and nucleic acids. Do these elements serve any specific purpose-or is this association an artifact of experimentation? Is the fact that metals are now being found as part of nucleic acids real? Many other questions can be raised.

Which metals are normally part of the nucleic acid complex; which are abnormal? Do the abnormal metals modify the rate of formation of nucleic acids, and especially the part of the nucleic acid that is responsible for carrying the genetic information? Cancer cells are reproduced extensively with no apparent limits. Do these abnormal metals help produce altered nucleic acids with different responses to known enzymes? What evidence is there that metals do serve a specific role in the structure and function of nucleic acids?

Polynucleotide phosphorylase, the enzyme which reversibly catalyzes the synthesis of polyribonucleotides from ribonucleo-side-5'-diphosphate, requires divalent magnesium, and the same ion must also be present for the incorporation of deoxy-ribonucleoside-5'-triphosphate into deoxyribose nucleic acid. Magnesium ion, therefore, in addition to being an essential part of at least fifteen different enzyme systems, as discussed in the previous section, must have an important role in nucleic acid synthesis, and even reactions. More than this, magnesium must play a part in holding subunits of polynucleic acids together.

Magnesium was found in all preparations of nucleoproteins regardless of method of preparation. Abnormally high molecular weights were found for polynucleotides made in a magnesium-enriched media. This element may be involved in combining the nucleoprotein 40S particles with those of 60S to make the 80S particle found in microsomes.

Calcium binds to DNA and RNA, similarly to magnesium. The plant Tradescantia paludosa grown in a calcium-deficient media had nine times higher frequency of chromosomal aberrations than did normal cells, and these cells had increased genetic sensitivity to x-rays. After treatment with phosphate salts, sea urchin sperm chromosomes were broken into rods of dimensions 4000 A X 250 A; this may possibly be only a salt effect, however. When drosophila were treated with EDTA, an increase of crossover frequency occurred. This effect was reversed by magnesium or calcium. Different types of chromosome breaks were noted in Vicia faba after EDTA treatment. In other studies with plant materials, heavy metal complexing agents like 8-hydroxyquinoline had similar effects. Chelating agents also induced abnormalities of meiosis and mitosis in flowering shoots. The organization of chromosomes depends on both magnesium and calcium ions.

In addition to magnesium and calcium ions, zinc and even copper are believed to be components of nucleic acids. The latter element was identified also in RNA in yeast and in the tobacco mosaic virus. In this TMV preparation, iron was found to be present in equal or greater amounts than copper. The strong electron spin resonance signal found in DNA may now be recalculated as a ferromagnetic constituent, and iron, if not an impurity, may be present in DNA in quantities of 1018 atoms per gram. Chromium, nickel, and manganese were detected in nucleic acid preparations from phyloge-netically different sources. A suggestion was made that these ions may help maintain configuration of the RNA.

From sedimentation rate studies of RNA in various salt solutions, conclusions were drawn that metals like nickel or manganese can either change the shape of nucleic acid molecules or influence the type of association of subunits into polymers.

Monovalent cations catalyze the incorporation of tritium-labeled thymidine into DNA. Potassium ion stimulates the normal incorporation rate by a factor of three. How many other enzymes are influenced by or dependent upon sodium or potassium?

In summary: Metals like magnesium may be involved in nucleic acid synthesis and reactions. Both calcium and magnesium may hold sections of chromosomes together and thus function to bind smaller nucleic acid units into larger asymmetric particles of high molecular weight. Transition metals may aid in keeping the configuration of RNA and may act as an intermediate to keep proteins bound to RNA. The site of binding may be the purine or pyrimidine bases.