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DNA repair 2

Let's continue to explore the fascinating world of DNA damage and repair. It explains how UV rays can cause pyrimidine dimers, leading to structural damage in DNA. The video also distinguishes between mutations and DNA damage, and explores both endogenous and exogenous factors that can cause DNA damage. Finally, it discusses the process of nucleotide excision repair and the potential consequences of faulty repair mechanisms.


Created by Efrat Bruck.

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Video transcript

- There are certain things that can cause damage to the structure of DNA, and one example of that is UV rays. And so, before we get into the damage that UV rays cause, let's just focus for a second on the key that I drew here on the left, and it's just to help us remember which colors represent which nitrogen bases. So, yellow represents the nitrogen base thymine. The orange bases represent cytosine. The green bases represent adenine, and the blue bases represent guanine. And so back to our DNA that's being damaged. If you look over here, there are two thymine bases that are kind of stuck together, and that's called a pyrimidine dimer. So, a dimer is simply when you have two molecules that are identical that are stuck to each other, and pyrimidine tells us that it can be two thymines that are stuck together, or it can be two cytosines that are stuck together. And UV rays cause the formation of pyrimidine dimers. And so you can see that the pyrimidine dimer actually is causing the sugar phosphate backbone to protrude, or kind of stick outwards, and not just that, but because the backbone is sticking outwards, the bond between this cytosine and this guanine snapped. So, you can see that there's some structural damage that happened to the DNA. And so, what are some factors that can cause damage to DNA? And, I want to just make a clear distinction between a mutation and DNA damage. So it's not the same thing. A mutation is when you have a change in the sequence of DNA. So, for example, if we had a piece of DNA that read ATCG, and then something happened and it read AACG. So this A is in the wrong place. That is a mutation. But when we talk about DNA damage, we're talking about damage to the structure of DNA, but the nucleotides are actually in the correct order. And so, DNA damage can be caused by Endogenous, or internal factors, and that means factors that originate within us, within our own cells. So, for example, there are certain byproducts of metabolism that can cause DNA damage, or DNA damage can be caused by Exogenous, or external factors, and those are factors that originate outside of us, or outside of the organism that we're discussing. So let's start with Exogenous factors first. So, we spoke about one of them, UV rays, and there are a lot of Exogenous factors that cause DNA damage, but we're just gonna list a few. Gamma rays can cause DNA damage. X-rays, and so that's why it's not healthy to be exposed to a lot of these rays. And, now let's talk about some Endogenous factors. So, reactive oxygen species is an example of an internal factor that can cause DNA damage. In a reactive oxygen species are molecules that contain oxygen and they're highly, highly reactive. So, there are a lot of different kinds of reactive oxygen species, but we're just gonna give two examples. So, for example, a super oxide anion, which is O2 with a negative charge. So let's just draw that. It's two oxygen atoms that are bound together, but there's one extra electron. And I'm actually gonna draw the extra electron in a different shade of purple, and so this whole molecule has a negative charge. So that's a reactive oxygen species. Another example would be peroxides. So peroxides are molecules that have two oxygens, and on either end, there's another atom. So that R can represent different types of atoms. So this is the general way that a peroxide looks. You might've heard of hydrogen peroxide. So this is hydrogen peroxide. And so where are these reactive oxygen species in our cells coming from? So actually, reactive oxygen species are a normal byproduct of the electron transport chain in the mitochondria. So there are a lot of reactive oxygen species all over our cells, but, fortunately, we have many enzymes that help protect against the damaging effect of reactive oxygen species. And, you may have heard of the term antioxidant, and so, an antioxidant is a molecule that also helps protect us against the damaging effect of reactive oxygen species. You may have heard that certain foods are really healthy because they have a lot of antioxidants, and that's true. So, vitamin C, for example, is an antioxidant. Vitamin E, and there are many, many different types of antioxidants, but we're just gonna give these two as an example. And so now that we've discussed some of the sources of DNA damage, let's go back to our damaged DNA and see if there's a way to fix this. So our cells can get rid of the pyrimidine dimers in a process called nucleotide excision repair. And so, the first step in nucleotide excision repair, is an enzyme, an endonuclease, is going to remove the pyrimidine dimers and any other nucleotides that are kind of not the way they're supposed to be. And so I just want to pause for a second and analyze that word. So, nuclease tells us that it's an enzyme that's able to cut out nucleotides, and that prefix endo tells us that it's able to cut out nucleotides from within a DNA molecule. That's in contrast to an exonuclease that can only take out nucleotides that are at the beginning or end of a DNA molecule. But anyway, the endonuclease is going to cut out the dimer and any other nucleotides that are not properly arranged. So let's just cut out all these nucleotides. The next step is a DNA polymerase, I'm just going to abbreviate that p-o-l, is going to come and bring the nucleotides that belong there. And then the last step is DNA ligase is going to make sure that those new nucleotides are attached properly to the nucleotides on either side and also the nucleotide that's complementary on the other strand. And so, that was a mouthful, but let's actually just draw all of that. So let's get rid of our backbone that's kind of protruding and just not right. So let's redraw our backbone. Something like that, or actually, draw it a little bit closer, and then, DNA plumerase brings the correct nucleotides, but remember, it's the ligase that actually connects the nucleotides properly. And so here's our corrected DNA. But, what happens if, for some reason, the nucleotide excision repair is not working properly, and this repair mechanism is only one example, there are many different types of DNA damage that can occur, and many different types of repair mechanisms. What happens if, for some reason, one of these, or a couple of these, are not working properly? Then, we get a cell that has a lot of damaged DNA. And there are three things that can happen to a cell like this. The first is it might go into this dormant state, where it just ages and does not divide any more. That's called senescence. The second thing that might happen to it is what's called programmed cell death, or apoptosis, and that basically means that the cell's going to commit suicide and die. And the third thing that might happen is the cell might start to divide uncontrollably. So I'm gonna write unregulated cell division. And this can cause cancer. And so actually, the skin cancer melanoma is an example of this. Melanoma, that's an n, melanoma happens when the nucleotide excision repair mechanism that we just discussed is not working properly, and so you have this accumulation of pyrimidine dimers that damages the DNA very much, and then the cell starts to divide uncontrollably.