The role of deoxyribonucleic acid in ribonucleic acid synthesis. IV. The incorporation of pyrimidine and purine analogues into ribonucleic acid.

The synthesis of ribonucleic acid from ribonucleoside triphosphates by an enzyme system dependent on deoxyribonucleic acid has been described (2-7). The base composition of the RNA produced is identical with that of the DNA which is added. This result can be attributed, by an analogy with the complementary base model of DNA structure proposed by Watson and Crick (8), to hydrogen bonding by successive bases in the DNA with complementary bases of the ribonucleoside triphosphate substrates prior to their enzymatic incorporation onto the RNA chain. Using DNA primers that contained unequal amounts of the complementary bases, Hurwitz et al. (9) obtained support for such a mechanism. They showed first that polyriboadenylate was formed in a reaction primed by polydeoxyribothymidylate. Furthermore, they found that DNA from bacteriophage +X 174, which Sinsheimer (10) showed to contain more adenine than thymine and more guanine than cytosine, directed the synthesis of RNA containing more uracil than adenine and more cytosine than guanine. In support of such a role of hydrogen bonding during replication of DNA catalyzed by DNA polymerase, Bessman et al. (11) have shown that base analogues of the four common deoxynucleoside triphosphates are incorporated in place of the natural substrates provided that the chemical changes introduced do not affect the 6-keto, or amino, group that Watson and Crick had postulated to be involved in hydrogen bonding. We describe in this paper the preparation of a similar series of ribonucleoside triphosphates containing base analogues and show that the specificity of their incorporation by the RNA polymer&se is identical with that observed in the previously cited study of Bessman et al. Thus, a fundamental similarity exists between the mechanisms by which DNA primes the formation of either complementary DNA or complementary RNA. This study also relates to the role that RNA polymerase may have in the synthesis of different classes of cellular RNA. We