8.3
Lagging Strand Synthesis
During replication, the complementary strands in double-stranded DNA are synthesized at different rates. Replication first begins on the leading stran…
The complementary strands in double-stranded DNA replicate at different rates. On one strand, the replication process is continuous and fast; this newly formed daughter strand is called the leading strand.
On the other strand, the replication process is discontinuous, relatively slower, and starts slightly later; this daughter strand is known as the lagging strand.
DNA polymerase can only synthesize DNA in the 5' to 3' direction. Because of this, the leading strand is synthesized continuously.
However, DNA polymerase cannot synthesize DNA in a 3' to 5' direction on the lagging strand.
To deal with this problem, DNA synthesis is carried out discontinuously in a 5' to 3' direction.
The enzyme DNA primase, which is present close to the opening of the replication fork, will synthesize multiple RNA primers on the lagging strand as the DNA unwinds.
Then, DNA polymerase synthesizes DNA onto the end of the primer until it encounters the next primer.
This cycle of primer synthesis by primase and subsequent DNA elongation by polymerase continues along the lagging strand. The resultant short DNA fragments are known as Okazaki fragments.
The enzyme RNase H then removes the RNA primers interspersed between the Okazaki fragments.
Another DNA polymerase then fills the empty spaces left after the removal of the RNA primers.
However, the DNA polymerase cannot fill the nicks present between Okazaki fragments.
This final task is performed by the enzyme DNA ligase, which joins the 3’ end of one fragment with 5’ end of another in order to make the discontinuous lagging strand into a continuous one.
Q1: Why is lagging strand synthesis discontinuous during DNA replication?
The lagging strand is synthesized discontinuously because DNA polymerase can only add nucleotides in the 5' to 3' direction. Since the lagging strand template runs 3' to 5', polymerase must work in short fragments called Okazaki fragments, moving away from the replication fork rather than continuously toward it.
Q2: What are Okazaki fragments and how long are they?
Okazaki fragments are short DNA segments synthesized on the lagging strand during replication. In prokaryotes, they are approximately 1,000 to 2,000 nucleotides long, while in eukaryotes they are much shorter, typically 100 to 200 nucleotides. These fragments are later joined together to form a continuous strand.
Q3: How does the replisome coordinate leading and lagging strand synthesis?
The replisome contains multiple DNA polymerases and accessory proteins that work together at the replication fork. The replisome components and the trombone model explain how the lagging strand template loops back, allowing both strands to be synthesized simultaneously despite their opposite directionality, maintaining efficient replication.
Q4: What enzymes are involved in completing lagging strand synthesis?
DNA polymerase I removes RNA primers left by primase and fills gaps with DNA nucleotides. DNA ligase then seals the remaining nicks between adjacent Okazaki fragments, creating a continuous phosphodiester backbone. This process ensures the lagging strand is fully synthesized and properly joined.
Q5: How does lagging strand synthesis differ between prokaryotes and eukaryotes?
Prokaryotic Okazaki fragments are 1,000 to 2,000 nucleotides long and synthesized by DNA polymerase III, while eukaryotic fragments are 100 to 200 nucleotides and synthesized by DNA polymerase delta. Eukaryotes also require additional processing due to chromatin structure and more complex replication machinery.
Q6: What happens if errors occur during lagging strand synthesis?
Errors during lagging strand synthesis can lead to mutations if not corrected. DNA polymerase has proofreading ability to catch mistakes immediately, and mismatch repair systems can identify and fix errors after synthesis. These mechanisms maintain genetic accuracy across cell divisions.
Q7: Why is understanding lagging strand synthesis important for DNA repair?
Lagging strand synthesis creates multiple vulnerable points where errors and damage can occur due to frequent primer removal and fragment joining. Understanding this process is essential for comprehending how repair mechanisms identify and fix damage, and how DNA damage can stall the cell cycle if replication is disrupted.