METABOLISM OF NUCLEIC ACIDS.

Abstract

Enzymatic synthesis of nucleic acids. Template function of primers.-With few exceptions, observations on DNA-synthesizing enzymes support base complementarity (1 , 2) as the code for the template function of their primers. Extension of this coding principle to DNA primers of DNA-dependent RNA polymerases provides strong evidence for the concept of messenger RNAs (3) . These concepts continue to be fruitful, but certain findings require modification or at least flexibility in the formulation of the original postu­ lates. Largely unknown is the detailed mechanism of the interactions which result in the final correlation between the structures of the template and those of the product, i .e . , in the respective code. In the absence of evidence for the intermediary formation of covalently linked compounds between template and precursors, various physical ap­ proaches and criteria are being explored, as base complementarity has been observed in complexes formed nonenzymatically between simple purine and pyrimidine derivatives (4, 4a) as well as between polynucleotide chains of high molecular weights. The specificity of the nonenzymatic interaction be­ tween two complementary polynucleotide strands (or perhaps between com­ plementary portions of two strands) is illustrated by the nonenzymatic for­ mation of at least three types of complexes between respective comple­ mentary polynucleotide chains: (a) renaturation of heat-denatured DNA double strands, (b) hybrid formation between single-stranded deoxyribo­ polynucleotide chains containing complementary purines and pyrimidines other than the four principal DNA-constituent bases (e.g . , hybrid formation between the strictly alternating copolymer of deoxyadenylic and deoxy­ thymidylic acids and the strictly alternating copolymer of deoxyadenylic and deoxy-5-bromouridylic acids), (c) hybrid formation between complementary deoxyriboand ribopolynuc1eotide chains. This type of hybrid was discovered by Rich (5), who demonstrated inter­ action between r-poly A and synthetic deoxythymidylate oligonucleotides on the basis of hypochromicity and sedimentation behavior. Schildkraut et al . (6) obtained hybrids between r-poly C and d-poly G by annealing. They ob­ served that the resistance of complementary complexes between riboand deoxyribopolynucleotide chains against ribonuclease is an important cri­ terion for hybrid formation. Presumably owing to the requirement of com­ plementarity, certain natural RNA specimens hybridize only with homol­ ogous, but not with heterologous, DNA. On this basis, Spiegelman and his