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 is replicated by continuous synthesis of a leading strand and discontinuous synthesis of a lagging strand of the DNA molecule.
Coordination between leading and lagging strand synthesis is achieved by the dimerization of DNA polymerase molecules at the replication fork.
The DNA polymerase dimer moves with the replication fork. The polymerase at the leading strand template remains attached to the DNA, continuously synthesizing the leading strand.
The lagging strand polymerase initiates DNA synthesis at the fork, from an RNA primer made by a primase complex.
The polymerase elongates the lagging strand in a direction opposite the fork, but stays bound at the fork. As a result, the newly synthesized lagging strand fragment loops out between the polymerase and the fork.Once the polymerase completes an Okazaki fragment, it dissociates from the DNA template. A new primer is produced at the fork. The polymerase reassociates with the template at this position, to continue synthesis of the lagging strand.
By this mechanism, the two polymerases can add nucleotides to the growing strands at the same time, and at rates up to 1000 base pairs per second.
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.