Which combination best explains the high fidelity of DNA replication?

• A. Correct base pairing, proofreading by 3'→5' exonuclease activity, and post-replication mismatch repair.
• B. Mismatch repair alone ensures replication accuracy.
• C. Base-excision repair during replication removes damaged bases.
• D. Nucleotide-excision repair guides replication accuracy.

Answer: (A)

High fidelity during DNA replication comes from multiple safeguards that operate at different times. The first line is the precise base pairing that guides nucleotide selection, so the correct base is continuously chosen opposite the template. Next, the DNA polymerase has 3'→5' exonuclease proofreading, which immediately detects and removes mispaired or misincorporated nucleotides as synthesis proceeds. Finally, the mismatches that escape proofreading are caught after replication by the post-replication mismatch repair system, which scans the new strand and repairs remaining errors. Together, these layers dramatically lower the error rate beyond what base pairing or any single repair mechanism could achieve alone. In contrast, base-excision repair and nucleotide-excision repair address DNA damage in general and are not the primary mechanisms that ensure the high accuracy of copying during replication; mismatch repair alone would miss errors that proofreading removes, and those damage-repair pathways don’t directly enhance replication fidelity.