Why doesn't DNA make mistakes? (Why does A not pair up with C?)

Key points:

Cells have a variety of mechanisms to prevent mutations, or permanent changes in DNA sequence.

During DNA synthesis, most DNA polymerases "check their work," fixing the majority of mispaired bases in a process called proofreading.

Immediately after DNA synthesis, any remaining mispaired bases can be detected and replaced in a process called mismatch repair.

If DNA gets damaged, it can be repaired by various mechanisms, including chemical reversal, excision repair, and double-stranded break repair.

Introduction

What does DNA have to do with cancer? Cancer occurs when cells divide in an uncontrolled way, ignoring normal "stop" signals and producing a tumor. This bad behavior is caused by accumulated mutations, or permanent sequence changes in the cells' DNA.

Replication errors and DNA damage are actually happening in the cells of our bodies all the time. In most cases, however, they don’t cause cancer, or even mutations. That’s because they are usually detected and fixed by DNA proofreading and repair mechanisms. Or, if the damage cannot be fixed, the cell will undergo programmed cell death (apoptosis) to avoid passing on the faulty DNA.

Mutations happen, and get passed on to daughter cells, only when these mechanisms fail. Cancer, in turn, develops only when multiple mutations in division-related genes accumulate in the same cell.

In this article, we’ll take a closer look at the mechanisms used by cells to correct replication errors and fix DNA damage, including:

Proofreading, which corrects errors during DNA replication

Mismatch repair, which fixes mispaired bases right after DNA replication

DNA damage repair pathways, which detect and correct damage throughout the cell cycle

Proofreading

DNA polymerases are the enzymes that build DNA in cells. During DNA replication (copying), most DNA polymerases can “check their work” with each base that they add. This process is called proofreading. If the polymerase detects that a wrong (incorrectly paired) nucleotide has been added, it will remove and replace the nucleotide right away, before continuing with DNA synthesis

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