Replication

The coordinated synthesis of the two daughter strands posed an important problem in DNA replication. The two parental strands of DNA run in opposite directions, one from the 5′ to the 3′ end, and the other from the 3′ to the 5′ end. However, all known DNA polymerases catalyze DNA synthesis in only one direction, from the 5′ to the 3′ end, adding nucleotides only to the 3′ end of the growing chain. The daughter strands, if they were both synthesized continuously, would have to be synthesized in opposite directions, but this is known not to occur. How, then, can the other strand be synthesized?

The resolution of the problem was provided by the demonstration that only one of the two daughter strands, called the leading strand, is synthesized continuously in the overall direction of fork movement, from the 5′ to the 3′ end (see Figure 3). The second daughter strand, called the lagging strand, is made discontinuously in small segments, called Okazaki fragments in honor of their discoverer. Each Okazaki fragment is made in the 5′ to 3′ direction, by a DNA polymerase whose direction of synthesis is backwards compared to the overall direction of fork movement. These fragments are then joined together by an enzyme called DNA ligase.