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In vivo studies'-7 of chromosome replication have led to the inference that both daughter strands of chromosomal DNA grow continuously, the direction of synthesis being 3' to 5' on one strand and 5' to 3' on the other (Fig. 1A). No enzymatic mechanism for the biosynthesis of deoxypolynucleotide in the 3' to 5' direction has been demonstrated, although 5' to 3' in vitro synthesis of DNA is accomplished by DNA polymerase.8 If discontinuous synthesis of DNA could occur in vivo (Figs. 1B-D), short stretches could be synthesized by a reaction in the 5' to 3' direction and subsequently connected to the growing polynucleotide chain by formation of phosphodiester linkages. It is possible to distinguish between continuous A B and discontinuous chain growth by elucidating the structure of the most recently replicated

Mechanism of DNA chain growth. I. Possible discontinuity and unusual secondary structure of newly synthesized chains.