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How Often Does DNA Polymerase Make A Mistake?

DNA polymerase enzymes are extremely precise, but even they are not perfect. Errors happen, and with these enzymes, they occur at a rate of about 1 per every 100,000 nucleotides.

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DNA replication is a complicated process, and it is to be expected that sometimes mistakes happen. However, cells possess a wide array of mechanisms that allow them to edit and fix these mistakes. DNA polymerase enzymes are extremely precise, but even they are not perfect.

Errors happen, and with these enzymes, they occur at a rate of about 1 per every 100,000 nucleotides. This is not that often, but it is not rare either. Our cells divide a countless number of times, not only during our development. They do it even while we are adults. Let’s explore what exactly happens during this process and how mistakes appear and get fixed.

DNA Replication

Whenever a human cell divides itself, and its DNA gets replicated, the cell needs to copy the same sequence of 3 billion nucleotides to the cells that are being created. You can imagine how hard it must be to do that perfectly every single time. Some mistakes are bound to happen during this process. Sometimes, the polymerase enzymes might insert the wrong nucleotide into the new cells. At other times there may be too many or too few nucleotides being placed into the sequence. 

Multiple processes are used to repair this, however. Those processes are referred to as DNA repair processes. There are special enzymes used during these processes that reconstruct any imperfection that may have occurred. They are capable of removing the wrong nucleotides and inserting the right ones in their place. It is an extremely precise mechanism that leaves little room for mistakes. However, there are some mistakes that even the DNA repair processes miss, and they become permanent.

Permanent Mutations

The mistakes that are not fixed on time become permanent mutations that are then passed down to the next cellular generation. If these permanent mistakes happen in cells that create the enzymes called gametes, they can keep getting transmitted to more and more generations. Another thing that can happen is that DNA repair enzymes become mutated. Once this happens, mistakes start happening more often. These types of mistakes often lead to cancer.

During DNA synthesis, the DNA polymerase enzymes are especially particular when it comes to their choice of nucleotides. They take care that everything gets paired up correctly. However, as we previously mentioned, they do make mistakes, and they happen in about 1 per every 100,000 nucleotides. That might not seem like something worth mentioning, but it is actually common enough that it can make a difference.

Consider the fact that humans have 6 billion base pairs in every one of their diploid cells. This means that whenever a cell divides, there are around 120,000 mistakes. This would be a huge problem if there were not ways to fix the majority of these issues. The large majority of them get fixed right away through a process called proofreading. The others get corrected after the process of replication is done, and that process is called mismatch repair.

The process of proofreading happens during replication, and in it, DNA polymerase enzymes find the wrong nucleotides and replace them with the right ones, continuing the replication process. Mismatch repair is used once replication is complete, and it is used to reduce the rate of errors completely. Enzymes can fix all of the deformities that happened by replacing the wrong nucleotides with the right ones.

About the Author

Antonia is a sociologist and an anglicist by education, but a writer and a behavior enthusiast by inclination. If she's not writing, editing or reading, you can usually find her snuggling with her huge dog or being obsessed with a new true-crime podcast. She also has a (questionably) healthy appreciation for avocados and Seinfeld.

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