In this video, we're going to continue to talk about DNA repair by focusing specifically on mismatch repair. And so when proofreading by DNA polymerase fails to correct a mutation, which can occasionally happen, the cell will then resort to mismatch repair. Now mismatch repair is a DNA repair mechanism, as its name implies, is going to fix mismatched nucleotides. And it does this by removing and then re-synthesizing regions of DNA. Now recall from our previous lesson videos that the DNA template strand can actually be distinguished from the newly built DNA strand via methylation, the addition of a CH3 functional group. And so recall that the old DNA template strand is going to be methylated, whereas the newly built DNA strand is not yet methylated. And so, the methylation helps enzymes distinguish between the old template strand and the newly built DNA strand.
Now mismatch repair occurs in a series of 4 steps that we have numbered down below in our image. And so, this image is focusing on mismatch repair. And in the very first step of mismatch repair, what you'll notice is we have the template strand is on the bottom here, and notice the old template strand is methylated, so it has these CH3 groups. And then the newly built DNA strand is at the top, and it is not yet methylated. And what you'll notice is that the incorrect nucleotide is going to be mismatched during DNA replication. And so, notice here in the DNA we have a mismatched nucleotide highlighted here in yellow. And so, this mismatch that you see right here, recall that Gs are supposed to be base-paired with Cs, not with As, and so this is a mismatched nucleotide.
So then in step number 2, a specific enzyme is going to cut the new DNA strand near the mismatch site. And again, the enzyme can distinguish between the new and the old DNA strand because, again, the old DNA strand, the template is methylated, but the new DNA strand is not yet methylated. And so it's going to cut the new DNA strand as you see here at a site near the mismatch. And then in step number 3, this enzyme is going to remove a short stretch of the new DNA strand, and this is going to include the mismatched nucleotide. And so notice here that the short stretch, a short region has been removed and that includes the mismatched nucleotide.
And then what happens is the DNA polymerase enzyme is able to come back into play and synthesize a new DNA fragment. And the new DNA fragment we've color-coded here in a reddish color just so that you can visually identify it. And so, the new DNA fragment is going to contain the correct nucleotide, and so it would have repaired that mismatch. And then a DNA ligase enzyme is going to come and seal the new fragment to create a single molecule. And so what you have here is the new DNA fragment has repaired that mismatch and now there is a C here when previously there was a mismatch, and there was an A, and so this is basically the fundamental steps of mismatch repair.
And so that concludes our brief lesson on mismatch repair and once again we'll be able to get some practice applying these concepts and learn about other DNA repair mechanisms as we move forward in our course. So I'll see you all in our next video.
