[0:14]What's up, Ninja Nerds? In this video today, we're going to be talking about the structure of DNA, but before we get started, please continue to support us by hitting that like button, commenting down in the comment section, and please subscribe.
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[0:36]All right, Ninja Nurse, let's get into it. All right, Ninja Nurses, when we start talking about the structure of DNA, before we do that, we have to have a nice little conversation about the nucleus because that's where DNA is housed.
[0:45]So let's have a quick little dive into the structure of the nucleus, what are the components within the nucleus, and what are the basic functions of what they do.
[0:52]First thing in here, here's we see the nucleus, and you have this blue structure, a double membrane kind of structure, a phospholipid bilayer if you will, and this phospholipid bilayer is referred to as your nuclear envelope.
[1:07]And we'll go over all the different components of that. Okay, the next thing is within the nuclear envelope, you have these little proteins that are nuclear kind of core complex that allow for certain things to be able to move to and from the nucleus and into the cytoplasm.
[1:20]And this structure right here is very important and these are called your nuclear pores. Okay, and they're usually made up of proteins, which help with the transport of things to and from the actual cell, uh cytoplasm and nucleus.
[1:34]The next thing I need you guys to know is inside of the actual nucleus is a big component of a bunch of stuff.
[1:40]And that bunch of stuff that's inside of it, all the stuff inside is called the nucleoplasm, and there's a couple different components to the nucleoplasm that we're going to go into great detail in.
[1:56]Okay, and this is the one that we'll pretty much focus on, but again, we have the main components here that we need to know for the structure of the nucleus.
[2:03]Now, first thing, nuclear envelope, remember I told you that there's two components, there's an outer membrane and an inner membrane.
[2:08]That's the thing I need you to know. This outer membrane, this component right here is what's kind of having ribosomes studded around the outside.
[2:18]Okay, so the next thing is your outer membrane, the thing I want you to associate with the outer membrane is where the ribosomes will be because what will happen is MRNA will come out of these nuclear pores near the outer membrane, bind with a ribosome, and then get translated to the rough endoplastic reticulum, and then that's where translation protein synthesis will occur.
[2:40]The next thing is the inner membrane. The inner membrane is very important, and there's a particular pathology that can be involved with the inner membrane that I want you guys to know for your USMLEs.
[2:54]And what is that? The inner membrane contains a very important protein, I want to draw this one out here in pink because of this pink filamentous protein that's on the inside.
[3:00]This inner membrane kind of provides a structural framework for the actual nucleus and allows for interaction with chromatin where genes are expressed and also undergo replication.
[3:10]And this protein is called lamins. There's lamin proteins. And why do you guys need to know that is that there's a mutation within a particular type of lamin called lamin A, and what happens is, if it's absent, it causes individuals, patients who are have this disease, to age very, very quickly, and it's called progeria.
[3:32]Okay, the next thing is your nuclear pores. Your nuclear pores are very straightforward. What do they do? They allow for things to move out of the nucleus into the cytoplasm and from the cytoplasm into the nucleus.
[3:44]What would we need for that? Just give me one quick example of something that would be going out via the nuclear pores. Really quick one, MRNA.
[3:52]MRNA would be one that's kind of leaving the nucleus because we need this MRNA to go out into the cytoplasm and get translated by the ribosomes.
[4:04]All right, so give me an example of something coming into the nucleus. What do we need to make DNA? That's a perfect example. You know, you synthesize nucleotides within different areas of the cell.
[4:14]What if I bring in nucleotides? That could be a very simple reason of why I need this little transport protein or nuclear pores to move things in and out of the nucleus. Really simple example, right?
[4:27]It's meant to be basic. The next thing is the nucleoplasm. In the nucleoplasm, there's two primary things that I want you guys to know. The first one here, we're going to call color coordinate is this big circular like little checks mix looking thing.
[4:40]This thing is called your nucleolus. This is one of the components of the nucleoplasm. What I want you to know is in the nucleolus, this is where your RRNA synthesis occurs.
[4:51]So you have some DNA in the area of the nucleolus, and what's happening is getting is getting transcribed and making RRNA. Also, you're making some subunits, some ribosomal subunits.
[5:05]And the reason why is, when you make RRNA, which is an a nucleic acid and you make subunits, which are your proteins, and there's different types of subunits, there's a large ribosomal subunit and a small ribosomal subunit.
[5:18]The combination of these two is what gives you your ribosomes, okay? And that's what I want you guys to remember. So what I tell you guys is that in the nucleolus, what is happening there? Ribosomal synthesis.
[5:32]And you know what's actually really interesting? Ribosomes are just small enough that they can fit through the nuclear pore, okay?
[5:41]And so that also is another thing that can be shuttled out. All right, so the next component of the nucleoplasm is your chromatin. And this is what I really want us to focus on because this is where DNA is.
[5:49]So chromatin, I need you to remember that this is made up of two different things that we'll discuss in a little bit more detail. One is what's called histone proteins, okay?
[5:59]These are very important and the other one is your good old DNA. Now, these two combos are what make chromatin, but chromatin's also a little bit special.
[6:06]And we'll talk about how, but histones and DNA, their combination works in a particular way because of their positive, negative attraction, that it condenses DNA into really, really compact structures that can fit within a nucleus in our in our cells.
[6:24]DNA is really long. And if I can condense it, I can fit a bunch of DNA inside of my nuclei.
[6:31]So, what happens is, chromatin can get condensed down into two forms. One of the forms is the highly condensed, H, highly condensed, I want you to remember heterochromatin.
[6:47]Heterochromatin, what I want you to associate with this with? Highly condensed. In other words, this is so condensed where the histones and the DNA have such a strong attraction with one another, that it's really hard for little enzymes to get in there, transcribe the DNA and make RNA.
[7:02]So what would happen with this? There would be no transcription in this type of chromatin.
[7:12]Very, very important, very high yield. The next thing is there's another type of chromatin, but this one is euchromatin. And remember that E, it's expressed.
[7:23]So this is a loose chromatin and I like to remember E for expressing. What does that mean? It's expressing. It's there's a weak attraction, there's a lax kind of relaxed attraction between the histones and the DNA.
[7:38]And because of that, there's nice space where the uh DNA, the RNA polymerases can get in there and make RNA. And so this occurs because we want this portion of the DNA to be able to undergo transcription.
[7:54]So again, big difference between heterochromatin is highly condensed, does not undergo transcription. Euchromatin is loose chromatin or expressing chromatin, meaning that you can transcribe it and make RNA.
[8:09]Get it? Very important. Okay, the last thing I want you guys to know is that chromatin, whenever our cells are undergoing a lot of replication, they want to allow for that chromatin to get passed on to the daughter cells.
[8:19]So your parent cell has to pass on the DNA to daughter cells. And so the way it does that is the chromatin during cell replication, it condenses down into what's called chromosomes.
[8:35]And that is where I want us to kind of take a quick little second here and understand DNA a little bit more is looking at how chromosomes, a really condensed structure of chromatin contains loops and loops and loops of DNA wrapped around histone proteins.
[8:54]And what's the significance of that? Let's move on to that part. All right, so we talked about how chromatin is made up of DNA, histone proteins.
[9:00]And whenever the cells are starting to replicate, they need to condense their chromatin down so that they can easily pass their genetic material onto the daughter cells. So what I want you to recognize is this right here is our chromosome.
[9:10]And what I want us to do is I want to yank all of that chromatin out of the chromosome and look at it deeper and deeper to the microscopic level.
[9:22]Okay, so once I take my chromosome, I'm going to start yanking some of the DNA out of this. As I yank some of the DNA out, it kind of comes out in this loopy kind of continuous fiber.
[9:32]So I have my chromosome, I yank some of it out and then I get this loopy kind of continuous fiber that you're going to see here. After I continue to keep kind of going a little bit and I keep getting into the smaller and smaller versions of it, as I'm looking deeper into the structure, then it starts to get tight helical fibers.
[9:50]Okay, so we get tight helical fibers. So we got loopy continuous fibers, tight helical fibers. And then what happens is, you can't really see it that well, but they're in there. I'm going to draw some little red circles and little red dots in there.
[10:07]You start seeing these red structures that the DNA is kind of wrapping around. And that's where we get to zoom in on them because there's a significance that we need to kind of talk about a little bit.
[10:24]So now, we're going to take and zoom in on this little structure here because there's a significance that we need to kind of talk about a little bit. So we know that DNA is wrapped around this kind of big, reddish structure.
[10:31]What did I tell you chromatin was made up of? DNA, histone proteins. Let's take a quick second to understand the significance of this.
[10:36]So here's our DNA, we're kind of zooming in on it, and then the next component is this red structure here, and this is a histone kind of octamer.
[10:46]What the heck is an octamer? So octamers, you know, there's eight, there's eight of something. And there's particular histone proteins and I, and it's really quick that I want you guys to know this.
[10:55]There's what's called H2A, H2B, H3, and H4. And so if you count these up, right, there's four of these, so what do I have to have? Double of everything.
[11:10]To make an octamer. So I'm going to have two of each one of these things, and the combination of all of these, 2, 4, 6, 8, these components, the H2A, H2B, H3, H4, they make up an octamer.
[11:25]And all of these H's are histones, okay, they're proteins. What do I really need you to focus on with this? Histones have particular amino acids called lysine and arginine.
[11:39]And the significance of these is that lysine and arginine are positively charged amino acids. Very important that you guys remember that. Okay, why?
[11:51]Because DNA, and we'll talk about what is making DNA negative a little bit later, but DNA has a negative charge. So DNA has, I'll tell you quick, its phosphate groups within the DNA that creates a negative charge.
[12:05]So these histone proteins, they all have positive charges. And so because they have all these positive charges around them, what happens to opposite charges? They attract one another.
[12:16]So then the lysine and arginine on the histones will interact with the phosphate groups on DNA and tightly compact with one another. And that's what allows the DNA to get really nice and condensed. That is why I really need you guys to know that.
[12:28]There's a particular name for whenever the DNA wraps twice around this octamer of histone proteins. You know what this is called? We call this a nucleosome.
[12:39]So we call this a nucleosome. Why am I spending some time mentioning the significance of the nucleosome and these histone proteins? I'll tell you why.
[12:51]The reason why is histone proteins and DNA can be modified via the process of epigenetics. We're not going to get into a lot of detail in that, but I want to just quickly brush over this because there is permanence to this for your USMLEs.
[13:02]So there's concepts of what's called epigenetics, where you control or regulate the expression of genes throughout, I know, the lifetime from parental to daughter cells and and and so on and so forth.
[13:16]And how we do this is by we modify the DNA, okay? And we'll talk about this one.
[13:30]And the next thing that we can do is besides modifying DNA, is we can modify histone proteins, and this is the one that's a little bit more significant. With modifying DNA, within DNA, there's a specific thing that you can do.
[13:44]Let's say here I have a quick strand of DNA. And in the DNA, there's particular nucleotides called cytosine and guanine. These are located in these areas here.
[13:55]We're going to put CG, CG, CG. These areas where there's a lot of cytosine and guanine are called CpG islands. And what happens is, we can use different types of enzymes.
[14:07]And what these enzymes do is, they add methyl groups onto wherever these cytosine and guanine pro areas are. You know what that does whenever you add methyl groups onto these CpG islands?
[14:20]It basically inhibits this area of DNA from being able to be expressed. If you can't express a particular part of DNA, can you transcribe it, make MRNA, and then make proteins?
[14:29]No. That is important. So what I want you to remember is epigenetically, we can modify the DNA by methylating what's called, what are these little things here called?
[14:41]We call them CpG islands, areas of lots of cytosine and guanine. We methylate them and what is the response to this? This inhibits gene transcription, very important. So that's one way that we can control which genes we want to be expressed in particular cells.
[15:04]In our liver cell, we're going to make a particular protein. In the other cell, like in our brain, we might not want to make that particular protein. If we methylate that gene, that's what determines the differences.
[15:15]Pretty, makes sense, right? Same thing with the histone proteins. If we take, for example, those histone proteins and we actually kind of wrap some DNA around it.
[15:23]Here, I'm going to have a histone proteins like this. DNA here, and then inside of this is going to be your histone proteins. Right now, the histone proteins and the DNA are really tightly interact with one another. Not a chance in heck a little enzyme can get in there and transcribe the DNA there where that histone protein is occupying.
[15:47]So, what I can do is, I can use special little enzymes. And what these enzymes do is, they add on what's called an acetyl group. Okay, they can add on an acetyl group. And when I add on the acetyl group, it does something very, very interesting.
[16:03]What does it do? Let me show you. It takes this interaction between the DNA and the histone proteins and makes it really lax. Okay, we'll leave this one alone because we're going to talk about that in a second. But now, look, the histone protein between the DNA, there's a lot more space.
[16:21]If there's a lot of space now, what can happen? I can now have my little RNA polymerase enzyme get in there and transcribe the DNA that where that histone protein is occupying.
[16:34]So this can be transcribed. So transcription can occur here. Now, let's say I take another situation.
[16:45]Where instead, I'm going to put a methyl group on that histone protein. Okay, so now what I'm going to do is I'm going to put a methyl group onto that histone protein. Now, here's the thing that's interesting. If I only add in one methyl group, just one methyl group, okay, we'll put that here, it can perform the same type of effect as acetylation.
[17:05]Just one. So what I'm going to do is I'm just going to put one methyl group here. It can perform the same type of action as acetylation where it can relax the interaction between the DNA and the histone proteins, allowing for transcription.
[17:27]But if instead, I add on two to three of these actual histone proteins, then what's going to happen? I'm going to really tighten up the interaction between the DNA and the histone proteins.
[17:43]And there's not a chance in heck that the RNA polymerase can get in there and transcribe the DNA. So remember, if I add two to three methyl groups, what's going to happen? It's going to repress gene transcription, inhibit the gene from being transcribed, making RRNA, proteins, so on and so forth.
[18:03]So the result of this is you inhibit transcription. The last thing I want to mention here is that you can get the same kind of effect with this high amounts of methyl groups that you're adding on, if what if I just took and I used a particular enzyme.
[18:24]Okay, where I have what's called a deacetylase. And what I did is I had this deacetylase inhibit or remove the acetyl group. If I remove the acetyl group, what happens?
[18:37]Am I going to allow for a relaxation of the DNA and the histone proteins? No, they're going to be tightly compacted with one another. What happens? Transcription is inhibited.
[18:50]This is really important, I really need you guys to remember this stuff, okay? That covers our kind of epigenetic aspect of this.
[19:39]Now, let's get back over here, one quick thing before we move into the kind of the really small units of DNA, is there's one more histone protein.
[19:48]You're like, dang it, another one. You see this brown one here? This brown histone protein is actually probably one of the most important histone proteins. And this brown one is called H1.
[20:02]This is the H1 linker protein. So this is actually a linker protein. It links the DNA nucleosomes between one another. You see how it's doing that? Here's one linking this nucleosome to this nucleosome, this one to this one.
[20:14]So it's a linker protein. And because it's a linker protein, guess what? It has to be the most positively charged histone protein. So it has the most positive charge associated with it so that it can really condense down the chromatin.
[20:32]That's very important. Okay, now, let's keep going down. We've hit our nucleosomes hard. And we've discussed how we see two wraps of DNA around the histone proteins.
[20:39]As we start really kind of zooming into the DNA around the histone proteins, what do we start getting? We start getting this kind of double helix structure. And in this double helix structure, as we keep going down and down and down, we really start getting into the the like the actual microscopic components of these.
[20:56]And what are these components? And this is what we have to focus on, which is very important. One is this kind of backbone here. You see this backbone that I'm shading in blue? This is called your sugar phosphate backbone.
[21:14]And obviously, as you can tell, it's made up of what's called a ribose sugar and a phosphate group. And then the other component is these little colorful things inside.
[21:24]And these are called your nitrogenous bases. And there's different types of nitrogenous bases that we'll discuss because there's there's a lot of high yield stuff associated with that.
[21:37]But the combination of your sugar phosphate backbone and your nitrogenous bases are what makes up what's called a nucleotide. And then a bunch of nucleotides together make up a nucleic acid.
[21:51]So when someone says, what is DNA, you can just say, it's a sequence of nucleotides that are made up of sugar, phosphate, and nitrogenous bases.
[22:05]Now let's dig into each of these different constituents of DNA. All right, so the next thing I want you guys to know are what are the constituents, what makes up these nucleotides?
[22:11]And this is actually kind of the easiest part. Thank goodness, right? You're like, oh, I needed this. So here's what I want you guys to remember. Easy, simple stuff.
[22:18]If I have two rings, what's called a heterocyclic ring, okay, two of them, I'm representing two boxes here. This makes up particular types of nitrogenous bases.
[22:33]And these are referred to as your purines. And there's two different types of purines here. One is referred to as adenine, and the other one is referred to as guanine.
[22:50]So that's the first thing I need you guys to know. So two rings for these nitrogenous bases, two heterocyclic rings makes up what's called your purines, and that's made up of adenine and guanine.
[23:01]The next thing is the red one. The red one, if you just have one ring, a single ring structure, this makes up what's called pyrimidines. And your pyrimidines are made up of two, like there's actually three, but we're only talking about this for DNA.
[23:17]So there's actually technically three pyrimidines. I'll put it down, but I'm going to refer to it only in RNA. This is particular to DNA. The three types of pyrimidines, you can remember by cut pie.
[23:27]Cut pie, pyrimidines, remember, cytosine, uracil, and this is the only one that is not in DNA, it's only in RNA. All these other ones are going to be in DNA.
[23:41]And then thymine. Okay, these are going to be your nitrogenous bases. And again, two rings, purines, single ring pyrimidines. If you're trying to hard time separating them, cut pie is going to be cytosine, uracil, thymine, that makes it pyrimidines.
[23:59]The remaining two are adenine and guanine. Okay. Now, that's one component we talked about. The next component is the pentose sugars.
[24:08]The pentose sugars, I want you to remember that this is a a ring sugar and usually it's in the form of what's called two different types. One is you have what's called a oxyribose, but we're just going to put it as ribose.
[24:20]And the other one is called deoxyribose. And believe it or not, there's not much of a difference between these. It's really one just atom that's different. And what happens is, you have this structure here.
[24:34]I'm just giving you the basic structure. This is your basic structure here. At this point here, this is your number one kind of carbon here. And what happens is, well, actually right here, but what happens is this is what connects to your nitrogenous base.
[24:50]This is your number two carbon, this is your number three carbon, this is the number four carbon, this is the number five carbon. It's actually very important for you to remember primarily three and five.
[25:05]Okay. On the two carbon, this is what really makes the difference. And ribose, there's an OH. And deoxyribose, which we'll talk about in a second, there is no OH, it's just an H.
[25:17]The next thing I need you guys to remember here, is on the three carbon, every three carbon, whether it be ribose or deoxyribose, there's an OH group. On the fourth carbon, nothing, on the fifth carbon, this is where I need you to remember the next structure.
[25:31]And that next structure we're going to draw here in orange, is going to be where the phosphate group will combine onto. Okay, so that's where the phosphate group is. I'm just trying to give you the significance of the ribose sugar.
[25:40]So, three group, OH, five group, phosphate. Two group, if it's ribose, has an OH group, first carbon has the nitrogen. If it's a deoxyribose, it's literally the same thing structure. The only thing that's different is what, guys?
[25:59]I know you guys are yelling it out. H, there's no OH there. Okay, that's why it's oxy versus deoxy, right? Pretty straightforward. On the third carbon, what's here? OH.
[26:10]On the fourth carbon, nothing. CH2, which is your fifth carbon, what comes off of that fifth carbon? You guys remember, it is the phosphate group, which is connected with the fifth carbon. Okay?
[26:23]So this is going to be our ribose sugars or our pentose, pentose meaning it's a five carbon sugar. The main things I need you to remember, five carbon has phosphate, three carbon has OH group.
[26:34]Difference between oxyribose and deoxy is the OH on the second carbon, H on the second carbon for deoxyribose. The next thing is the phosphate group.
[26:44]The phosphate group is really where we really need to remember that this is where it's the negatively charged structure. Okay, so here's our phosphate group. Okay? Now, phosphates are important because of that negative charge, because that's what allows for the DNA, the negative charge of DNA to interact with histone proteins.
[27:02]So what do I need to know? Is just this basic structure of phosphate is found on what carbon? First thing I need you to know is that it's a very negatively charged, so that allows for that interaction with DNA and histones.
[27:14]And the second thing is it binds to what carbon? The fifth carbon on the pentose sugar. Can't stress that enough. All right, the next thing I need you guys to know, is there's a couple nomenclature terms that I want you guys to know.
[27:31]We're not going to go into crazy detail because it can kind of be confusing. We'll talk about them more in the purine and pyrimidine synthesis pathways. But I want you to know the difference between a nucleoside and a nucleotide.
[27:41]The basic difference, if we just take, for example, I take one nitrogenous base and I take one pentose sugar, doesn't matter, that's all a nucleoside is.
[27:51]Is I'm just going to have this structure here. I'm going to have my pentose sugar. And my phosphate there. And what do I have coming off here? Let's just say I have a purine. I have adenine.
[28:07]So if I just have what two structures? That is what makes up a nucleoside. What are the two components? A pentose sugar and a nitrogenous base. That is what makes up a nucleoside.
[28:33]Now, a nucleotide is all of these things. So that's where I want us to finish up. A nucleotide is now, let's build this whole thing up here.
[28:40]I have my pentose sugar. I have my OH on my third carbon. We're talking about DNA, so we need just a deoxyribose. My one carbon, let's just put here again, adenine or guanine, I'm putting a purine ring.
[28:55]And then again, what do I have coming off here on my fifth carbon? I have that phosphate group. If I have all of these things, what components? A phosphate group, a pentose sugar and a nitrogenous base. This is what makes up a nucleotide.
[29:16]We now have a basic concept of this. These do have different names. I don't want to get too bogged down into that. What I want you to know the difference between a nucleoside, no phosphate, nucleotide, phosphate.
[29:28]Simple as that. Now that we know that, let's take a bunch of nucleotides, string them together, and start making our DNA. So now, what I need us to start talking about here is kind of taking these nucleotides, stringing them up together, interacting with one another and making our DNA.
[29:40]Because that's what we know that nucleotides make up nucleic acids and DNA is one of them. Before we do that, we have to have a quick little discussion on the concept of complementarity.
[29:51]And this is honestly, it's like a super easy thing. Let's say I take, for example, my purines and I draw these out here. My purines, I'm going to have my adenine, which I'm just going to represent often as represented as A. The other one is going to be my guanine, often represented as G.
[30:08]The next thing you guys need to know is that adenine and guanine have to have an interaction with some of these purines. What are those interactions? And that's very important here.
[30:20]Adenine loves to interact with thymine. And guanine loves to interact with cytosine. But there's a very significant thing that I want you guys to remember.
[30:30]These interactions is the basis of your complementarity. These are going to interact with one another. And the way that they interact with one another is actually very important. We're going to do it here, represented in blue.
[30:43]There's what's called hydrogen bonds that link these different, uh, uh, nitrogenous bases together. Between guanine and cytosine, and adenine and thymine. And these hydrogen bonds that I need you guys to remember is that for adenine and thymine, there is two hydrogen bonds.
[30:59]So what should that tell you a little bit? That should tell you that it's probably easier to break the bonds between adenine and thymine than it is to break the bond between guanine and cytosine. That comes into particular play with DNA replication, that's why I'm telling you that.
[31:13]The next thing is, here we have three hydrogen bonds. So a little bit more difficult to break the bond between guanine and cytosine. But the big thing I need you guys to remember is that hydrogen bonds are weak bonds.
[31:26]They're kind of these electrostatic interactions, but again, these are weak bonds. You know what's a really strong bond? Another type of bond between the phosphates and the other the hydroxyl group, and that's the one I want to talk about now.
[31:43]So let's say that I take my nucleotide, what's a nucleotide? Test your knowledge. A phosphate group, a pentose sugar, and a nitrogenous base. I'm going to string them up in a line.
[31:52]When you look at DNA, DNA has this concept of what's called a antiparallel type of arrangement. So it has what kind of arrangement here? It has an anti-parallel arrangement.
[32:07]And what that means is that on one end, let's say on this left side, it's arranged from five to three. And again, you guys know what that means. We'll explain it in a little bit in a second. That means that the right aspect, in this case, let's say this is the left part of the DNA, the right part of the DNA.
[32:21]On this right side, it has to be arranged in the opposite direction, going from top to bottom, which means it has to be arranged in a three end to five end fashion. That's the concept of anti-parallel DNA.
[32:41]So it's moving in, it's basically oriented in opposite directions of one another. Now, let's explain this complementarity aspect with this anti-parallel strand.
[32:51]Let's pretend that this pink structure here, this is a nitrogenous base. Let's say that this is adenine. On this left strand, we want it to interact with this actual nitrogenous base on the right strand.
[33:02]According to complementarity, which one would it have to be? It would have to be thymine. Same concept here. Let's say that this one is, which one? Let's say that this one is thymine, which nucleotide, or which nitrogenous base would this one have to be according to complementarity? Adenine.
[33:20]Let's use the next concept. Let's say that this pink one here is guanine, which nucleotide do you think it would have to be according to complementarity? Cytosine.
[33:37]And then for simplicity or to be, you know, complete, how many bonds here? 1, 2, 3, 1, 2, 3, 1, 2, 1, 2 hydrogen bonds. The next concept here is this backbone.
[33:50]Remember, I told you that there's what's called a sugar phosphate backbone. That's the next thing I need you guys to know. Here's what's called a sugar phosphate backbone.
[34:04]This sugar phosphate backbone is important because it's made up of a particular bond called a phosphodiester bond. And this is a very, very powerful bond, a very, very strong bond.
[34:18]Covalent bond if you will. So I want you to remember this is a strong bond. And it's formed, again, I told you we're going to come back to this five end, three end thing, but this strong bond is formed between the five end of one and the three end of another nucleotide.
[34:34]What's on the five end? Do you guys remember? What do we say was on this five end? The phosphate group. We're just going to represent here as our phosphate group.
[34:42]Okay? What do we say was always on the three end? Here, we'll write it down just for your simplicity's sake. This one is your five end, this is your three end. What was on the three end again? The OH group.
[34:52]I'm going to form a bond between these two structures here. And when I do that, that bond between the five end and the three end of one nucleotide is what makes a phosphodiester bond, a very strong bond.
[35:33]Isn't that cool? Now, that kind of gives us the basic concept here of what DNA looks like. Sequence of nucleotides, held together by phosphodiester bonds, interacting anti-parallel fashion via hydrogen bonds dependent upon the concept of complementarity.
[35:54]And one strand is moving from five to three. This would be your five end, that would be your three end. And the other one is moving in the opposite direction, being a three end to five end for that anti-parallel fashion.
[36:06]Now, let me take this DNA, because this is not how, um, a, let me take this DNA, because this is not how DNA looks like. It doesn't in a perfect world when you're drawing it out.
[36:15]But it's actually kind of has a three-dimensional shape where it starts kind of looping and looping and looping, creating this double helix if you will. So now here we have the DNA, right? And the DNA is in this form of a double helix.
[36:26]And there's a couple things, there's actually multiple different types of DNA, not a chance we're going to talk about that because it can be kind of complicated and it's not worth it. So double helix is this kind of anti-parallel fashion, but in a three-dimensional shape where you see the DNA kind of winding around in this way.
[36:42]When it does that, it creates these little grooves if you will. This groove right here is a big old groove. And this groove right here that I want you to know is called the major groove.
[36:55]Okay, it's called the major groove. It's just kind of the anatomy and the topology of DNA. Then, you have another groove, but this groove is a little bit tinier because of the way that the DNA folds.
[37:05]And this groove is actually the one that I really want us to know about, which is called the minor groove. And the minor groove is important because guess what? A lot of enzymes which are going to replicate DNA or transcribe some of the DNA, particularly replicate the DNA, bind onto this portion here.
[37:25]If I give a drug called dactinomycin, dactinomycin kind of sits within that minor groove, and what does it do? It inhibits the DNA from being able to replicate.
[37:37]Imagine it kind of just sitting there, and an an enzyme has to kind of jump into this portion to kind of go and replicate this DNA strand, it can't because it's being blocked by what thing? Dactinomycin. Let's pretend that dactinomycin is this pink structure, just kind of sitting in this area here.
[37:52]And you want to bring an enzyme down to uh to replicate this DNA strand, but you can't because this is blocking it. So that's one of the significances that I need you guys to remember with respect to the kind of topology of DNA.
[38:05]And the last little fun fact that I'll give you guys, is that you see this whole portion here of the DNA before it makes this kind of turn to go into another little portion.
[38:13]This right here is made up of about 10 nucleotide base, like 10 nucleotides for each turn that you make, okay?
[38:21]So for each turn, 10 nucleotides and then another turn, 10 nucleotides. Okay? So again, this really gives us a lot of detail on our DNA structure, a lot of the interactions.
[38:33]Let's take a quick little second to appreciate how if there's any kind of pathology or certain drugs that we can use that can alter the structure of DNA or the organization of DNA.
[38:45]Let's talk about that quick. All right, so why did I kind of talk about all this stuff and really focus on those histone proteins really significantly? There was a reason why. There's a clinical relevance related to it that you guys can see on your USMLEs. Particularly related to drug induced lupus.
[38:56]So with lupus or SLE, right? There's a kind of a sub type of it. What happens is, in these individuals, their immune system, right? Their immune system, their plasma cells, generate antibodies.
[39:12]And these antibodies, they target particular things. You know what they target? They love to target those histone proteins. And whenever they target these histone proteins, it leads to a lot of kind of a destruction of particular cells and injury to a lot of cells.
[39:27]And that is why it's really important. So, whenever somebody has drug induced lupus, I guess the first question that you should have is what are the drugs that can precipitate this type of, you know, autoimmune like reaction?
[39:41]And you can remember this via the mnemonic ship. And it goes sulfanamides, hydrazine, isoniazide, which is commonly abbreviated IH, procainamide, which is an anti-rhythmic, and then an anti-convulsant known as phenytoin.
[40:11]These drugs can sometimes trigger an autoimmune reaction. So when you're testing for drug induced lupus, it's different from when you're testing for SLE. Even though this is kind of a type of SLE. In SLE, you test for anti-double stranded DNA, anti-SMITH DNA.
[40:22]In drug induced lupus, you're actually testing for anti-histone antibodies. Okay, so that is important to remember. The next particular thing that I need you guys to remember is Huntington's disease.
[40:37]Believe it or not, Huntington's disease can be related to issues with the, uh, histone proteins. You know how? What happens is, there's issues where in histone proteins, they have some issue with there's an an increase in what's called deacetylation.
[40:54]Remember what a deacetylation was, and there was a reason why I took the time to mention that. Do you remember what happens when you increase deacetylation? You remove acetyl groups.
[41:06]If you remove acetyl groups from the histone proteins, what did that do? It tightened up the interaction between the histone and the DNA. If you tighten up the interaction between the histone and DNA, can you transcribe it? No. What does that result in? It inhibits transcription.
[41:20]So it's going to inhibit or decrease transcription. You know why that is actually important? There's a couple reasons why. One is in nerves, okay, particularly nerves that are involved in our basal ganglia.
[41:35]They need to release, they need to transcribe particular proteins called growth factors, nerve growth factors. Because what these nerve growth factors do is, they help to stimulate nerve growth and repair and kind of some of that aspects of it, right?
[41:47]If I have some type of issue where I'm decreasing the transcription of growth factors that are helping with nerve growth, what's going to happen? I can lead to destruction of these nerves over time because they're not going to have the proper stimulus to continue to grow.
[42:01]So in that situation, this can lead to neuron, uh, injury and death. And you know where this is particularly type of important? Within the basal ganglia structures, within side of the central nervous system.
[42:19]And what happens is, there is injury to particular structures within the basal ganglia, and it causes a type of abnormal or hyperkinetic movement disorder. Does that make sense?
[42:40]So again, simple concept. Huntington's disease is related to an increase in deacetylation, decreasing transcription of growth factors, as well as there's transcriptional dysregulation of the, what's called the Huntington's protein and abnormal protein is produced.
[42:57]And it causes increased neuron injury and death, particularly where basal ganglia, and it results with hyperkinetic movements. Okay, the last thing that I want us to talk about here.
[43:06]Is that remember that we talked a lot about purines and pyrimidines and nucleotides and all their significances because they make up DNA. What if I inhibited the synthesis of these purines, these pyrimidines?
[43:21]Would I be able to make DNA? No. So there's drugs that I really want you guys to remember like anti-cancer drugs. Wouldn't that be a perfect reason why you definitely would want to like not allow for DNA to replicate as a cancer cell?
[43:34]If I gave anti-cancer drugs, or I gave drugs to uh individuals who have an infection and I actually inhibit the replication of bacteria, I inhibit the replication of viruses, I inhibit the replication of parasites.
[43:49]So, what would this be? Antibiotics, antivirals, and what else? It could also be um antiparasitics. And also, you know what else we use these for? Immunosuppressants.
[44:06]Inhibiting the replication of those immune system cells that are causing a lot of havoc on our body. That is important. And so what we can do is we can give drugs within these categories that can inhibit purine synthesis.
[44:20]To give you a couple, I don't want to spend a ton of time on these, but a lot of these are utilized. For example, uh, some that you may want to consider here in these situations would be like what's called six mercaptopurine.
[44:33]Another one is called azathioprine. Another one is called ribavirin. And another one is called mycophenolate. Six mercaptopurine and azathioprine, mycophenolate are primarily immunosuppressant drugs.
[44:53]Ribavirin is an antiviral. These would be things that would inhibit purine synthesis. What if I wanted to give a drug that inhibited pyrimidine synthesis?
[45:01]So I didn't want to make any of those pyrimidines. What kind of drugs would I give here? This would be things like methotrexate. This would be things like what's called trimethoprim, which is commonly used in what's called Bactrim, which is an antibiotic. Methotrexate is also used as immunosuppressant.
[45:20]Another one called pyrimethamine. Okay, so there's a bunch of them. And this pyrimethamine is actually an anti-parasitic. So you can use these different drugs to inhibit the synthesis of pyrimidines as well.
[45:34]And the last one is what if I wanted to inhibit the both of them? Purine and pyrimidine synthesis. There's a bunch of different drugs that can do that as well. One of the big ones that you guys want to remember here is hydroxyurea.
[45:49]Okay, so that gives us the most important clinical significance related to the structure of DNA. All right, Ninja Nurses, in this video today, we talk about the structure of DNA. I hope it made sense and I hope that you guys didn't enjoy it. All right, Ninja Nurses, as always, until next time.
