How is replication fidelity maintained during DNA synthesis?

• A. Fidelity is maintained by proofreading activity of 3'→5' exonuclease activity of DNA polymerases.
• B. Fidelity is achieved solely by post-replication mismatch repair.
• C. Fidelity is ensured by the helicase preventing mispairing.
• D. Fidelity is maintained by RNA primers correcting errors.

Answer: (A)

Fidelity during DNA synthesis comes mainly from the proofreading ability of DNA polymerases, which have a 3'→5' exonuclease activity. When a wrong nucleotide is added, the polymerase pauses, its exonuclease domain removes the mispaired nucleotide from the end of the growing strand, and synthesis resumes with the correct base pairing. This real-time proofreading dramatically reduces errors as replication proceeds. Even so, a few mistakes escape and are corrected later by post-replication mismatch repair, which scans the new DNA and fixes remaining mismatches, further boosting accuracy. Other proposed ideas, like helicase preventing mispairing or RNA primers correcting errors, don’t actively fix misincorporations during synthesis, so they don’t account for fidelity as effectively.