Short Segments of Newly Synthesized DNA Are Joined Into a Continuous Strand By What?
Short segments of newly synthesized DNA are joined into a continuous strand by DNA ligase. On the lagging strand, DNA ligase seals the gaps between Okazaki fragments by forming a phosphodiester bond between the 3'-OH of one fragment and the 5'-phosphate of the next.
The answer
The short segments of newly made DNA are joined into a continuous strand by DNA ligase. During replication, one new strand — the lagging strand — is built in short pieces called Okazaki fragments rather than in one continuous run. DNA ligase is the enzyme that stitches these fragments together, sealing the breaks in the sugar-phosphate backbone so the strand becomes one unbroken molecule.
Mechanically, DNA ligase catalyzes the formation of a phosphodiester bond between the free 3'-hydroxyl (3'-OH) group at the end of one fragment and the 5'-phosphate group at the start of the adjacent fragment. This bond is the same type of linkage that holds the rest of the DNA backbone together, so once ligase acts, the join is seamless.
Why the lagging strand needs ligase
DNA polymerase can only add nucleotides in the 5' to 3' direction, and the two template strands run antiparallel. The leading strand runs in the convenient direction, so it is synthesized continuously toward the replication fork. The lagging strand runs the opposite way, so polymerase must work away from the fork in short bursts, producing Okazaki fragments. Each fragment starts with a short RNA primer laid down by primase. Before the fragments can be joined, those RNA primers are removed and replaced with DNA — a job done by DNA polymerase I in bacteria (and by RNase H plus polymerase in eukaryotes). Only after the primers are replaced does DNA ligase seal the final nicks.
Why the other enzymes are not the answer
It helps to distinguish ligase from the other players at the replication fork:
- Helicase unwinds and separates the double helix — it does not join anything.
- Primase makes the short RNA primers that give polymerase a starting point.
- DNA polymerase adds new nucleotides to a growing strand and proofreads, but it cannot connect two separate fragments end to end — it leaves a nick between them.
- Topoisomerase relieves the twisting tension ahead of the fork.
Only DNA ligase forms the phosphodiester bond that closes the gap between fragments, which is why it, and not polymerase, is the enzyme that produces one continuous strand.
The bigger picture
DNA replication is a coordinated team effort: helicase opens the helix, primase primes, polymerase builds and proofreads, polymerase I swaps out primers, and ligase performs the final seal. Understanding ligase's specific role — joining the 3'-OH and 5'-phosphate ends of Okazaki fragments — makes clear why the lagging strand ends up just as continuous and intact as the leading strand. DNA ligase is also widely used in molecular biology and genetic engineering to join DNA fragments during cloning.
Short Segments of Newly Synthesized DNA Are Joined Into a Continuous Strand By What?
Frequently asked
What are Okazaki fragments?
Okazaki fragments are the short pieces of DNA synthesized on the lagging strand during replication. Because DNA polymerase only works in the 5'-to-3' direction, the lagging strand is built in these discontinuous segments, which DNA ligase later joins into one continuous strand.
What is the difference between the leading and lagging strand?
The leading strand is synthesized continuously in the 5'-to-3' direction toward the replication fork. The lagging strand runs the opposite way, so it is made discontinuously as short Okazaki fragments that are later joined together by DNA ligase.
Which enzyme removes RNA primers before ligation?
In bacteria, DNA polymerase I removes the RNA primers and replaces them with DNA. In eukaryotes, RNase H and other nucleases remove the primers and a DNA polymerase fills the gap. DNA ligase then seals the remaining nicks.
How does DNA ligase form a phosphodiester bond?
DNA ligase catalyzes a bond between the 3'-hydroxyl group at the end of one DNA fragment and the 5'-phosphate group at the start of the next. This phosphodiester linkage joins the sugar-phosphate backbone, using energy from ATP (or NAD+ in bacteria).