How Does DNA Proofreading Work?

DNA proofreading is an essential self-correction mechanism that ensures the incredibly high accuracy of DNA replication, preventing genetic errors and maintaining genomic stability.

The Vigilant Role of DNA Polymerase in Proofreading

During the process of DNA replication, the enzyme responsible for synthesizing new DNA strands, DNA polymerase, also functions as a highly effective proofreader. This built-in error-checking capability is crucial for maintaining the integrity of our genetic material.

Here's a step-by-step breakdown of how this remarkable process unfolds:

1. Base Addition and Immediate Check: As DNA polymerase adds each new nucleotide to the growing DNA strand, it doesn't simply rush to the next one. Instead, it meticulously reads the newly added base before proceeding to add the subsequent nucleotide.
2. Correct Pairing Verification: The polymerase then performs a critical check: it verifies whether the newly added base has paired correctly with its complementary base on the original template strand. For example, it ensures that adenine (A) is correctly paired with thymine (T), and guanine (G) with cytosine (C).
3. Error Detection and Correction: If an incorrect base has been incorporated – signaling a mismatch (e.g., A mistakenly paired with G) – the DNA polymerase immediately detects this error. At this precise moment, a correction can be made. The enzyme possesses an intrinsic 3' to 5' exonuclease activity, which allows it to snip out and remove the incorrectly paired nucleotide from the growing strand.
4. Resumption of Synthesis: Once the erroneous base is excised, the polymerase then inserts the correct nucleotide, ensuring proper base pairing. If the newly added base is indeed the right one, forming a perfect match with the template strand, the polymerase then moves forward to add the next nucleotide, continuing the synthesis of the DNA strand.

This real-time correction system significantly reduces the rate of replication errors, ensuring that genetic information is passed on faithfully from one generation of cells to the next. Without such a robust proofreading mechanism, the accumulation of mutations would be vastly higher, with severe implications for cellular function and organismal health.

The Impact of Proofreading on Replication Fidelity

The remarkable accuracy of DNA replication is largely attributed to proofreading. Without this mechanism, the error rate would be significantly higher, leading to numerous mutations.

This table highlights how proofreading dramatically improves the fidelity of DNA replication, reducing errors by a factor of 100-1000.