DNA replication fidelity: Which statement correctly describes the proofreading activity that maintains the accuracy of DNA synthesis in cells?

Introduction / Context:
High fidelity DNA replication is essential for genome stability. DNA polymerases not only synthesize new strands but also correct errors in real time. This question tests your understanding of the intrinsic proofreading mechanism associated with replication.

Given Data / Assumptions:

• Replication requires both polymerization and error correction.
• We compare on-the-fly proofreading versus post-replicative repair.
• Mechanistic detail: exonuclease directionality.

Concept / Approach:

Most replicative DNA polymerases possess 3'–5' exonuclease activity that removes a misincorporated nucleotide immediately after it is added. This backtracking and excision reduce error rates dramatically before mismatch repair acts. Proofreading is intrinsic to the polymerase holoenzyme in both prokaryotes and eukaryotes (e.g., E. coli Pol III, eukaryotic Pol δ and Pol ε).

Step-by-Step Solution:

Verification / Alternative check:

Mutations disabling the 3'–5' exonuclease increase mutation rates, demonstrating its role in proofreading apart from postreplicative mismatch repair pathways.

Why Other Options Are Wrong:

“Occurs after completion”: that describes mismatch repair, not polymerase proofreading.

“Requires separate enzyme”: proofreading is within the polymerase complex, not a separate nuclease.

“Occurs in prokaryotes but not eukaryotes”: incorrect; eukaryotic replicative polymerases also proofread.

Common Pitfalls:

Confusing proofreading (intrinsic, 3'–5' exonuclease) with mismatch repair (postreplicative pathway) or nucleotide excision repair (damage removal).

Final Answer:

It is a function of the 3'–5' exonuclease activity of DNA polymerases