What is the Difference Between Leading and Lagging Strand

The main difference between leading and lagging strand is that the leading strand is the DNA strand, which grows continuously during DNA replication whereas lagging strand is the DNA strand, which grows discontinuously by forming short segments known as Okazaki fragments. Therefore, to form a continuous strand, the leading strand does not require ligase while the lagging strand requires ligase to ligate Okazaki fragments together. Furthermore, the leading strand opens in the 3’ to 5’ direction while the lagging strand opens in the 5’ to 3’ direction.

Leading and lagging strand are two terms that we use to describe the two strands of the double-stranded DNA during DNA replication based on the pattern of strand growth.

Key Areas Covered

1. What is a Leading Strand
     – Definition, Type of Strand Growth, Importance
2. What is a Lagging Strand
     – Definition, Type of Strand Growth, Importance
3. What are the Similarities Between Leading and Lagging Strand
     – Outline of Common features
4. What is the Difference Between Leading and Lagging Strand
     – Comparison of Key Differences

Key Terms

DNA replication, Leading Strand, Lagging Strand, Okazaki Fragments, Replication Fork

What is a Leading Strand

Leading strand is one of the two strands of the DNA double helix. Generally, DNA undergoes replication during the cell cycle as a step of preparing the cell for the division. DNA polymerase is the enzyme that is responsible for DNA replication carried out exclusively in the 5’ to 3’ direction. During the process, each strand of the DNA double helix serves as templates for replication. Therefore, the process of DNA replication is known as a semiconservative process where each newly synthesized DNA double helix composes an old and a new DNA strand

Figure 1: DNA Replication.

During replication, the DNA double helix unwinds to form the replication fork. Here, the DNA strand, which opens up in the 3’ to 5’ direction allows the growth of the strand continuously in the 5’ to 3’ direction. Therefore, we call this strand as the leading strand. In the leading strand, DNA polymerase can add nucleotides continuously, and the growth of the new DNA strand occurs towards the replication fork.

What is a Lagging Strand

The lagging strand is the second strand of the DNA double helix. The strand opens up in the 5’ to 3’ direction. Therefore, the new strand growth has to occur away from the replication fork as the direction of DNA replication occurs only in the 5’ to 3’ direction. On that account, the replication process is not continuous, and it occurs through the formation of Okazaki fragments. Generally, Okazaki fragments are short segments of DNA, about 1000-2000 nucleotides long.

Figure 2: Continuity of the Leading and Lagging Strand

Also, at the beginning of each Okazaki fragment, an RNA primer has to be synthesized on the lagging strand. RNA primase is the enzyme responsible for the synthesis of RNA primers on the template DNA during DNA replication. The growth of the last Okazaki fragment stops at the 5’ end of the RNA primer of the former Okazaki fragment. Significantly, the DNA replication of the lagging strand always has a ‘wait time’ for the synthesis of a new RNA primer. Ultimately, the RNA primers are removed from the strand and DNA polymerase fills the missing nucleotides. Then, DNA ligase joins each DNA fragment together on the lagging strand, making a continuous DNA strand.

Similarities Between Leading and Lagging Strand

• Leading and lagging strand are the two types of DNA strands found in the double-stranded DNA molecule.
• They are classified based on the pattern of replication.
• However, the leading and the lagging strand are complementary to each other.
• Furthermore, both strands are made up of DNA nucleotides, which link to each other through phosphodiester bonds.
• Also, DNA polymerase is responsible for the synthesis of both leading and lagging strands.

Difference Between Leading and Lagging Strand

Definition

Leading strand refers to one of two strands of DNA found at the replication fork, being replicated continuously while lagging strand refers to the other strand found at the replication fork, replicating discontinuously in the 5′ to 3′ direction. Thus, this is the main difference between leading and lagging strand.

Type of Growth during DNA replication

Importantly, the leading strand grows continuously while the lagging strand grows discontinuously by forming Okazaki fragments.

The direction of the Template in the Replication Fork

Furthermore, another important difference between leading and lagging strand is that the leading strand opens up in the 3’ to 5’ direction while the lagging strand opens up in the 5’ to 3’ direction.

The direction of Strand Growth

Leading strand grows in the 5’ to 3’ direction while the lagging strand grows in the 3’ to 5’ direction.

Primers

Leading strand requires a single primer for the synthesis while the lagging strand requires a new primer to start each Okazaki fragment. Hence, this is another difference between leading and lagging strand.

The beginning of the Replication

Moreover, the starting point too contributes to the difference between leading and lagging strand. The leading strand starts to grow at the beginning of replication while the lagging strand starts to replicate shortly after.

Direction from the Replication Fork

Also, the leading strand grows towards the replication fork while the Okazaki fragments of the lagging strand grow away from the replication fork.

Speed of Formation

Additionally, the speed of formation is another difference between leading and lagging strand. The formation of the leading strand occurs at high speed while the formation of the lagging strand occurs slowly.

The requirement of DNA Ligase

Besides these, the leading strand does not require DNA ligase while the lagging strand requires DNA ligase to ligate Okazaki fragments together.

Conclusion

Leading strand is one of the two strands of the double-stranded DNA. Significantly, it opens up in the 3’ to 5’ direction at the replication fork. Therefore, it undergoes strand growth continuously in the 5’ to 3’ direction during the DNA replication. In comparison, the lagging strand is the other strand in the DNA double helix. However, it opens up in the 5’ to 3’ direction. Therefore, its strand growth has to occur in the 3’ to 5’ direction. But, usual DNA replication occurs in the 5’ to 3’ direction only. Hence, DNA replication occurs towards the outside of the replication fork discontinuously by forming Okazaki fragments. On that account, the main difference between leading and lagging strand is the direction and the pattern of strand growth.

References:

1. “What Is DNA Replication?” yourgenome, The Public Engagement Team at the Wellcome Genome Campus, 25 Jan. 2016, Available Here.

Image Courtesy:

1. “DNA replication en” By LadyofHats Mariana Ruiz – Own work. Image renamed from File:DNA replication.svg (Public Domain) via Commons Wikimedia  
2. “Timeline of replication for leading and lagging strand.” By Thermodynamic – Own work (CC BY-SA 3.0) via Commons Wikimedia