In DNA synthesis, new nucleotides are joined one at a time to the 3′ end of the newly synthesized strand. DNA polymerases, the enzymes that synthesize DNA, can add nucleotides only to the 3′ end of the growing strand (not the 5′ end), and so new DNA strands always elongate in the same 5′-to-3′ direction (5′→3′). Because the two single-stranded DNA templates are antiparallel and strand elongation is always 5′→3′, if synthesis on one template proceeds from, say, right to left, then synthesis on the other template must proceed in the opposite direction, from left to right (Figure 9.7). As DNA unwinds during replication, the antiparallel nature of the two DNA strands means that one template is exposed in the 5′→3′ direction and the other template is exposed in the 3′→5′ direction. So how can synthesis take place simultaneously on both strands at the fork?

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CONTINUOUS AND DISCONTINUOUS REPLICATION As the DNA unwinds, the template strand that is exposed in the 3′→5′ direction (the lower strand in Figures 9.7 and 9.8) allows the new strand to be synthesized continuously, in the 5′→3′ direction. This new strand, which undergoes continuous replication, is called the leading strand.

The other template strand is exposed in the 5′→3′ direction (the upper strand in Figures 9.7 and 9.8). After a short length of the DNA has been unwound, synthesis must proceed 5′→3′; that is, in the direction opposite that of unwinding (Figure 9.8). Because only a short length of DNA needs to be unwound before synthesis on this strand gets started, the replication machinery soon runs out of template. By that time, more DNA has unwound, providing new template at the 5′ end of the new strand. DNA synthesis must start anew at the replication fork and proceed in the direction opposite that of the movement of the fork until it runs into the previously replicated segment of DNA. This process is repeated again and again, so synthesis of this strand is in short, discontinuous bursts. The newly made strand that undergoes discontinuous replication is called the lagging strand.

OKAZAKI FRAGMENTS The short lengths of DNA produced by the discontinuous replication of the lagging strand are called Okazaki fragments, after Reiji Okazaki, who discovered them. In bacterial cells, each Okazaki fragment ranges from about 1000 to 2000 nucleotides in length; in eukaryotic cells, they are about 100 to 200 nucleotides long. Okazaki fragments on the lagging strand are linked together to create a continuous new DNA molecule. To see how replication occurs continuously on one strand and discontinuously on the other, view Animation 9.1.