Okay. So now let's talk about double-stranded breaks, which are a very serious type of DNA error and DNA mutation. Double-strand breaks occur when both strands are broken, and they can be repaired in two ways. The first is called non-homologous end joining. You may see it abbreviated as NHEJ. Essentially, it just takes the areas that are broken and sticks them back together. Proteins come in, they recognize, they say, "Oh, DNA damage has happened." Proteins come in, trim off the area, and DNA ligase just connects them back together. This type of repair occurs outside of the S phase. Now remember, the S phase is the point of mitosis where the DNA is replicated. Right? And, if the DNA is not actively being replicated, there's nothing else it can do other than just sort of stick it together. So non-homologous end joining occurs then, but obviously, that's not ideal, because whatever caused the break and whatever is missing due to the break is not repaired. You can end up with some serious gene distortions due to double-strand breaks.
The second form is homologous recombination, which we've gone over before in a different way in terms of recombining genes and crossing over during meiosis. But it can also be used to repair double-stranded breaks. Now, this occurs directly after replication because you have to have those extra copies to do it. What you do is you use sister chromatids that have now been replicated as a template to repair the broken strand. It's similar to crossing over, so the strand that's broken sort of invades the sister chromatid strand where the DNA is, and a DNA polymerase uses that as the template to repair it. But this is different from crossing over. Right? Because in crossing over, the non-sister chromatids are used, whereas in homologous recombination for DNA repair, the sister chromatids are used. And that's an important difference to understand. Homologous recombination for repair uses sister chromatids, whereas crossing over uses non-sister chromatids. This is also known as synthesis-dependent strand annealing. You'll see that potentially it's the same process. In non-homologous end joining, there's been a break, and they're just sort of glued back together, just sort of stuck back together through DNA ligase, and that can be very damaging because whatever was here before is now lost for good. Homologous recombination uses the breaks that occurred here. Right? There are the breaks. But these strands invade the sister chromatids and use that as a template to replicate and repair, so that you replace what has been lost. But again, this happens during replication because you have those extra sister chromatids to be able to do this with.
So with that, let's now move on.