DNA Repair

Hi in this video we're gonna be talking about DNA repair. So DNA damage occurs often and it's repaired in a lot of different ways. So one of the a couple of the ones that we've talked about previously. The first is DNA proof reading and DNA proof reading is just the process of repairing a nucleotide that has been added an error and so it prepares a miss pair base. And so this is one that we've already talked about and it's a major part in repairing that damage D. N. A. There are other ways um that are maybe less specific. We're gonna talk about individual pathways but I did want to throw this other pathway in and this is just that there are a lot of different enzymes that can reverse the image of D. N. A. So for instance um there's an enzyme CPD photo lice licenses and this is an enzyme that repairs die MERS calls from UV light so give you light, it hits our skin anytime we go outside. It's gonna cause diners. And there's these enzymes in there that go and repair this. Then there's enzymes for every type of specific D. N. A. Um and these kind of exists. I mean of course their pathways but they exist outside of the major pathways that we're gonna talk about later. So these are the kind of the first to just like summarizing different ways that D. N. A. Damage can be repaired. So here's an example of proof reading. We have D. N. A. Plymouth race. This is being copied. There's some type of error that happens here where C. Is paired with A. T. Not supposed to be proofread and goes back exercises at sea and makes the correct T. A. Pairing as it extends forward. So that is one major way that DNA damages repair. Let's turn the page and talk about more specific pathways.

Okay so now let's talk about some individual pathways that are that repair different types of specific damage. So the first is called the base excision repair or ber pathway. And this removes and replace damaged nucleotides. And so pretty much how this happens is there's a an enzyme called DNA glycol dialysis. They come in they say oh this D. N. A base is damaged and it cuts it out from the sugar backbone. When it cuts it out, there's another enzyme, the deoxyribonucleic bosco diess erase enzyme. I know it's a mouthful. I mean how many even letters are in there? It's a ton anyways, that enzyme comes in and it cuts out a section of DNA that's neighboring around the base. And then D. N. A. Plum race comes in, fills that gap with the correct nucleotides. And then DNA like comes in and seals that gap. So here we have damaged base in blue like a soulless comes and cuts it out. There's more things that come in cut out this big section and DNA polymerase comes in synthesizes that section and DNA like gaze comes in and repairs and make sure that comes in. So birds responsible for fixing a damaged base. We have a nucleotide excision repair. This is a repair that fixes damage that distorts the double helix. So we talked about different ways that the double helix can be distorted and if it is distorted that creates this like hump that varies proteins and enzymes like races can't overcome. So it has to be fixed so that the double helix is back to its normal structure there. So nervous responsible for that. There are two types. There's the global and transcription coupled, the global fixes anywhere in the genome and the transcription coupled fixes where active transcribed regions of D. N. A. Obviously because of their names, but they essentially work the same way. They may have different proteins but essentially are worth the same way. So there's some kind of damage based proteins recognize it. They recruit more proteins to the area. Each one of these proteins have different functions but that's for a more advanced class. Eventually a 30 nucleotide segment or around 30 nucleotides. It's not exact but just around 30 nucleotides is removed, then DNA polymerase fills in the gap DNA like seals it and then the distortions are fixed because the correct bases are there. Um nucleotide uh excision repair if there are defects in it or distortions here, but defects essentially. Um They can actually cause serious diseases including extra german pigmentosa and the syndrome here. And essentially these are those syndromes that may have referred to as light allergies. They're not actually allergies but they do have this sensitive to light because when the light comes in it can create distortion in the double helix like die MERS for instance UV light causes a lot of different timers and if you don't have a way to fix that, if you are defective in your nucleotide excision repair pathway than those diamonds stay and you end up getting a lot of cancers and rashes and lesions on the skin because your body can't repair the damage that the light causes, do it? So that's N. E. R. So here we have an example of this. You don't necessarily need to know the proteins but just understand there's some kind of problem that's happened here. It creates a distortion in the double helix. Um proteins come in recognize that distortion. Eventually this whole segment will be removed. D. N. A. Polymerase comes in, replaces it and lays comes in, seals the edges and repairs the pathway. And so that is how nature works. Then we have mismatch repair mismatch repair repairs damaged D. N. A. That occur for the assertions or deletions. And generally this occurs immediately following replications of some kind of replication error. So what happens is there's a mismatched base either from an insertion or deletion that has occurred and those they obviously don't complementary region. So there's gonna be mismatched um proteins come in that are specific for mismatch repair to recognize the um base. But then the problem comes in of which base is wrong, Right? Because if you have an insertion, you could have, you know, A. T. T. T. C. G. And C. A. R. Yeah. See A. G. Um C. Right. And this is obviously the mismatch, there's been an insertion here. But how do you know? Is it the A. Or is it the sea that has been mismatched. And so how the proteins figure out which one is actually the insertion of which one's mismatched wrong is by the meth immigration status of the D. N. A. Now remember D. N. A. Has histone proteins. Those histone proteins are methylated now only the old strand of D. N. A. Not the new strand that's just been replicated. Remember replication is important for this. Only the old strand has that methylation. The new strand that methylation has to be added onto it. And so methylated strand is the old strand um methylated as the new strand. So they use the UNM methylated strand and know that this one is the one with the mutation on it, where this one should be. The methylated strand should be used to repair that. So DNA collaborates then uses that methylated strand fills in the gap and DNA like seals it. So here we have the mess match the methylated isn't blue and methylated and brown or brown proteins come in um and repair this mismatch. Right there we go. Okay so those are three major types of DNA repair. But with that let's not turn the page

Okay so now let's talk about an unusual type of DNA repair called trans lesion synthesis. And so translation synthesis is a really poor DNA repair pathway and it's usually only used as a last resort. So there's nothing else the cell can do. But it's gotta it wants to prevent death. So it's going to use this pathway. And so what it does is typically these types of DNA damage that translation attempts to repair our DNA damage. That caused the D. N. A. Polymerase to stall on while it's replicating. And so if it can't continue replicating then the D. N. A. Is severely damaged. It can't replicate, it can't divide and that usually triggers the cell to kill itself. Now the sale doesn't want to kill itself. So if there's any way that it can keep this DNA polymerase going and keep replicating, it wants to use it. And so it uses this translation synthesis pathway. So what happens is if there's some kind of distortion, some mutation that causes the D. N. A polymerase to stall, then it sends in these extra plate races called trans lesion or bypass plummer races and they are recruited to the area. Now translation Plymouth races actually have the ability to overcome various helical distortions that caused the other polymerase to stall so it can't move but these ones can but we lose some efficiency with that because they have no proof reading so they can't fix anything that's wrong. They have a very high error rate and they only do a few nucleotides at a time before they fall off. So generally what happens is the replicating plum race. It stalls because there's some kind of DNA damage here in red. The translation plum race will come in and it will overcome this DNA damage. But then it falls off because it's not very good at what it does. And therefore the replicating Plymouth race is added back on and it keeps going generally how that works. And so it's it's good enough to overcome this distortion. But what it doesn't do is it doesn't fix the damage, right? That DNA damage is still there and now it's being passed on to another cellular generation. Um and it has a higher error rate and can cause mutations in addition to the one that's already existing that isn't repair because there's no proof reading. So this is a real, like I said, really poor, but it keeps the cell from death and that is what's important for the cell at this point because it doesn't want to die, but it needs to replicate itself. And so translation synthesis is what allows the cell to prevent itself from dying in the instance of mutations. So with that let's not move on.

Okay, so now let's talk about double stranded breaks, which are very serious type of D. N. A. Um error. And our DNA mutation. So double strand breaks occur is when both strands are broken and it can be repaired in two ways. The first is called non homologous end joining. You may see it as N H E. G makes sense. And essentially it just takes the areas that are broken and sticks them back together. So proteins come in, they recognize they say oh DNA damage has happened. Um proteins come in sort of trim off the area DNA like it's just connect them back together and this is the type of repair that occurs outside of s phase. Now, remember essays is the point of mitosis where the DNA is replicated, right? And um if the D. N. A. Is not actively being replicated, there's nothing else that 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 because the break happened is not repaired. So you can end up with some serious um gene distortions due to double shrimp breaks. Second form is homologous recombination, which we've gone over before in a different way in terms of recombining genes and crossing over during mitosis, 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 in order to do it. And so what you do is use sister chroma tides that have now been replicated because the cells replicating as a template to repair the broken strand. So it's similar to crossing over. So the strand that's broken sort of invades the sister chromatic strand where the D. N. A. Is and A D. N. A. Plane races use that as the template to repair it. Um But this is different than crossing over, right? Because in crossing over the non sister chromosomes are used. Whereas in homologous recombination for DNA repair, the sister chromosomes are used and that's an important difference. Um To understand homologous recombination for repair uses sister chromosomes. Whereas crossing over uses non sister chroma tides. And this is also you can see as synthesis dependent strand and healing. You'll see that potentially that it's the same process. So here we have 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 like ice. And that can be very damaging because whatever was here before is now lost for good homologous recombination uses. So the breaks occurred here, right? There are the brakes but these strands invade the sister chroma tides 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 chroma tides to be able to um do this with. So with that let's now move on

Which of the following repair pathways repairs damage that causes distortions in the double helix?

• A. Base Excision Repair
• B. Nucleotide Excision Repair
• C. Mismatch Repair
• D. Homologous Recombination

Which of the following repair pathways uses a methylated strand of DNA to correct DNA damage?

• A. Base Excision Repair
• B. Nucleotide Excision Repair
• C. Mismatch Repair
• D. Homologous Recombination

True or False:Translesion DNA synthesis is the first mechanism the cell uses to repair DNA damage?

• A. True
• B. False

Which of the following pathways is an error-free way to repair double-stranded breaks?

• A. Homologous recombination
• B. Non-homologous end joining
• C. Translesion synthesis
• D. Mismatch repair