In DNA replication, short Okazaki fragments are synthesized on the lagging strand, leaving small nicks (unsealed phosphodiester gaps) between adjacent fragments. Which enzyme finally seals these nicks to create one continuous DNA strand?

Introduction / Context:
During semi-conservative DNA replication, the lagging strand is copied discontinuously as multiple short DNA pieces called Okazaki fragments. After fragment synthesis and primer removal, the sugar–phosphate backbone still contains nicks. This question tests your understanding of which enzyme catalyzes the final joining step that restores backbone continuity.

Given Data / Assumptions:

• Lagging-strand synthesis generates multiple Okazaki fragments.
• RNA primers are removed and gaps are filled with DNA.
• Residual nicks remain between adjacent fragments until a specific enzyme acts.

Concept / Approach:
The key reaction is formation of a phosphodiester bond between a 3'-OH and an adjacent 5'-phosphate at a nick. The canonical enzyme for this ligation in cells is DNA ligase, which uses an energy cofactor (ATP in eukaryotes and bacteriophages; NAD+ in many bacteria).

Step-by-Step Solution:

Verification / Alternative check:
Historically, discovery of Okazaki fragments was paired with demonstrations that ligase-deficient systems accumulate nicks, confirming ligase as the essential sealing enzyme.

Why Other Options Are Wrong:

• DNA gyrase: relieves positive supercoils ahead of the fork; it does not seal nicks.
• RNA ligase: joins RNA; the nick here is in DNA.
• DNA polymerase I: fills gaps after primer removal but leaves a nick that must be sealed by ligase.
• Helicase (DnaB): unwinds DNA; no ligation function.

Common Pitfalls:
Confusing gap filling (polymerase) with nick sealing (ligase), or assuming topoisomerases repair breaks; topoisomerases manage supercoiling, not Okazaki nicks.

Final Answer:
DNA ligase