Biochemistry Questions Biochemistry Questions / Explain the significance of the active site structure in high fidelity DNA polymerases and how it impacts replication fidelity.

High-fidelity DNA polymerases have very tight and specific active sites. This prevents non-canonical base pairing from occurring. Occasionally Hoogsteen base pairs can occur, but virtually all nucleotides are incorporated under the rules of Watson-Crick base pairing.

By preventing non-canonical base pairing, these DNA polymerases maintain their high-fidelity, reducing the number of errors in the DNA.

Where an error is made, the polymerase has an exonuclease site, allowing it to remove the incorrect section and start again. This increases accuracy further.