Which enzyme synthesizes the short RNA primer required to initiate DNA synthesis on the lagging and leading strands at the replication fork?

Introduction / Context:
DNA polymerases cannot start synthesis de novo; they require a preexisting 3' OH to extend. Cells therefore use a specialized RNA polymerase, primase, to lay down short RNA primers that DNA polymerases can elongate.

Given Data / Assumptions:

• Replication forks operate on both leading and lagging strands.
• Primers are short RNA segments.
• DNA polymerase extends from the primer's 3' OH.

Concept / Approach:
Primase synthesizes RNA primers using ribonucleotides. On the leading strand, a single primer often suffices; on the lagging strand, each Okazaki fragment needs a new primer.

Step-by-Step Solution:

Verification / Alternative check:
Reconstituted replication systems without primase fail to initiate synthesis; adding primase restores initiation of both strands. In vivo, primase is part of the primosome with helicase.

Why Other Options Are Wrong:

• DNA helicase: Unwinds DNA but does not synthesize RNA.
• DNA ligase: Seals nicks after DNA synthesis; cannot start chains.
• DNA topoisomerase: Manages supercoiling; not involved in primer synthesis.
• Exonuclease I: Degrades single-stranded DNA; not a priming enzyme.

Common Pitfalls:
Assuming that because primase is an RNA polymerase it only works on the lagging strand; in fact it primes both strands as needed.

Final Answer:
Primase.