DNA Mismatch Repair: Correcting Errors That Happen During DNA Replication

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  • 0:05 DNA Repair
  • 0:58 Mismatch Repair
  • 1:51 Recognizing the Error
  • 2:30 Recognizing the…
  • 4:14 Mismatch Repair and Cancer
  • 4:44 Lesson Summary
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Lesson Transcript
Instructor: Katy Metzler

Katy teaches biology at the college level and did her Ph.D. work on infectious diseases and immunology.

Don't you love spell check? Well, our cells do, too. Their spell check is called mismatch repair. In this lesson, learn how cells use mismatch repair to correct typos that they might make while they replicate their DNA.

DNA Repair

We've been talking a lot about mutations, or changes in DNA sequences, and the effects they can have on cells. You can compare mutations to typos: all those misspelled words can really add up and make a DNA sequence into a bunch of gobbledy-gook. We've also talked about a few different ways that mutations can happen, namely when cells are exposed to chemical mutagens and irradiation. Mutations can also happen because of mistakes that are made when the cell replicates its DNA. Wow! How do cells even survive in the face of all these mutations?

Well, cells are pretty impressive creatures, as you may know by now. They have many different ways to fix mutations and other kinds of DNA damage and get the DNA sequence back to normal. In this lesson, we'll learn about mismatch repair, which is kind of like a cell's spell check. Using mismatch repair, cells can correct errors that happen during DNA replication.

Mismatch Repair

In mismatch repair, mistakes that happen during DNA replication are recognized, cut out and replaced. Pretty impressive, but how does it work?

You know that during DNA replication, the DNA double helix is unwound so that the DNA polymerase can use the parental strand of DNA as a template or recipe to figure out what sequence the new strand should have. It adds in nucleotides one by one, but how does it know which nucleotide to put in at each spot? It puts in the nucleotide that can base pair to the nucleotide across from it. For example, if there's an A in the parental strand, DNA polymerase will put in a T across from it.

But nobody's perfect, including DNA polymerase. Sometimes, it puts in the wrong nucleotide and then keeps going. This mismatched base pair causes a point mutation, which you can think of as a typo in the DNA sequence of the new strand.

Recognizing the Error

Luckily, cells have a spell check mechanism. They have a way to recognize those typos right away and fix them. The so-called mismatch repair machinery is a group of proteins that work together to carry out mismatch repair. First, these proteins have to search for telltale bumps in the backbone of the DNA.

Wait a minute, what bumps? Well, if DNA polymerase put in an incorrect nucleotide, the base pairing won't be as tight and cozy as it normally would, because the two bases don't stick together as nicely as they usually do. There's a little more space in between them because the hydrogen bonds that normally hold base pairs together won't be able to form.

Recognizing the Parental Strand

After the mismatch repair machinery recognizes a bump, it's going to scan the DNA strand in both directions until it finds something really important: methyl groups. These are little CH3's that decorate the DNA strand every thousand base pairs or so. What do methyl groups have to do with anything? It turns out that methyl groups are a way for the mismatch repair machinery to recognize the parental strand of DNA as opposed to the new strand. Only the parental strand has methyl groups because it takes a little while for the new strand to get methyl groups added on to it.

Why does this matter? Well, if there's a mistake in the new strand, you want to correct it, right? What you don't want to do is change the sequence of the master copy, that is, the parental strand, to match the mistake in the new strand. That would just be adding insult to injury; doing more damage rather than fixing the damage. So, it's important for the mismatch repair machinery to know which strand to repair and which strand to leave alone.

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