What Is the Difference Between the Leading Strand and the Lagging Strand in DNA?

During DNA replication, the leading strand replicates continuously, while the lagging strand replicates in fragments. This occurs because replication can only occur in the 5′ to 3′ direction, while one of the two strands is oriented 3′ to 5′ with the other being oriented 5′ to 3′.

DNA polymerase, an enzyme responsible for carrying out synthesis, adds nucleotides to an existing DNA strand in the opposite direction of that strand’s orientation. Thus, a strand must be oriented 3′ to 5′ so the enzyme can add nucleotides in the 5′ to 3′ direction. When DNA replication begins, small portions of the DNA double helix unwind at various points along the molecule called replication origins. Each opening is called a replication fork and serves as a spot where each strand of the DNA molecule can become a newly replicated molecule through the addition of nucleotides. Because each new molecule features one old strand from a previous molecule and one newly synthesized strand, DNA replication is said to be semiconservative.

The leading strand is oriented 3′ to 5′, meaning new nucleotides can readily be added in the opposite 5′ to 3′ direction without interruption. However, in the case of the lagging strand, which is oriented 5′ to 3′, DNA polymerase must add new nucleotides in the direction facing away from the replication fork. As replication continues, this fork continues to open more along the strand, so DNA polymerase must continually reorient itself, causing replication to occur in fragments.