During DNA replication, the replication of one of the two strands of DNA proceeds in a relatively straightforward manner. DNA polymerase adds nucleotides continuously, following directly behind the unzipping replication fork. However, the replication of the second strand is far more complex. Because the two strands of DNA are antiparallel, DNA polymerase must replicate them in opposite directions. Therefore, the replication of the second strand follows in a direction opposite the replication fork, and it does so discontinuously, replicating a segment of DNA at a time. The two strands of DNA are referred to as leading- and lagging-strands, respectively.


DNA polymerase replicates DNA by adding one nucleotide at a time to a growing DNA strand. Each nucleotide is complementary to the nucleotide in the template strand. Although DNA polymerase carries out this primary function of DNA replication, the enzyme has its limitations. First, the enzyme can only add nucleotides to an existing 3'-hydroxyl group. Second, the enzyme can only add nucleotides in one direction along a template strand: the 5' to 3' direction.

Addressing the need for a hydroxyl group, the primase enzyme starts the replication of a strand of DNA by synthesizing a short segment of RNA. This segment—called a primer—provides the required hydroxyl group and is later cut out and replaced by DNA.

The antiparallel nature of the two strands of DNA requires that the strands be replicated differently at the unzipping replication fork. The leading strand is replicated continuously, with the synthesized DNA growing in the 5' to 3' direction as it follows behind the replication fork. The lagging strand cannot be replicated continuously, because this would require that the synthesized fragment grow in the 3' to 5' direction—a function that DNA polymerase cannot perform. Therefore, the new strand is built in segments (Okazaki fragments), one at a time as new areas of lagging-strand template DNA are exposed by the unzipping replication fork. These segments are later linked by the enzyme DNA ligase, resulting in a continuous strand of DNA.

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Textbook Reference: Concept 9.2 DNA Replicates Semiconservatively