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 the comment section and please subscribe also down in the description box we have links to our facebook and instagram as well as our patreon you guys want to go to our patreon we'll have supplemental resources there that help engage you more in this learning process all right engineers let's get into it all right ninja nurse 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 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 first thing is here here's we see the nucleus and you have this blue structure a double membrane kind of structure it's a phospholipid bilayer if you will and this phospholipid bilayer is referred to as your nuclear envelope 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 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 cytoplasm and nucleus the next thing i need you guys to know is inside of the actual nucleus is a big component of a bunch of stuff 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 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 now first thing nuclear envelope remember i told you that there's two components there's an outer membrane and an inner membrane 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 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 endoplasmic reticulum and then that's where translation protein synthesis will occur 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 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 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 and this protein is called lamins there's lamin proteins and why you guys need to know this 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 have this disease to age very very quickly and it's called progeria 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 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 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 all right so give me an example of something coming in to 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 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 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 color coordinate is this big circular like little chex mix looking thing 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 r rna synthesis occurs so you have some dna in the area of the nucleolus and what's happening is it is getting transcribed to making rrna also you're making some subunits some ribosomal subunits and the reason why is when you make rrna which is 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 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 you know what's actually really interesting ribosomes are just small enough that they can fit through the nuclear pore okay 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 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 these are very important and the other one is your good old dna now these two combos are what make chromatin but chromatin is also a little bit special 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 dna is really long and if i can condense it i can fit a bunch of dna inside of my nuclei 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 heterochromatin what i want you to associate this with highly condensed in other words this is so condensed where the histones in 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 so what would happen with this there would be no transcription in this type of chromatin very very important very high yield the next thing is there's another type of chromatin but this one is u-chromatin and remember that e it's expressed 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 relaxed kind of relaxed attraction between the histones and the dna and because of that there's nice space where the 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 so again big difference between hetero is highly condensed does not undergo transcription euchromatin is loose chromatin or expressing chromatin meaning that you can transcribe it and make rna 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 cell 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 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 in loops of dna wrapped around histone proteins 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 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 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 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 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 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 you start seeing these red structures that the dna is kind of wrapping around and that's where we got to zoom in on them you see this red structure here where dna is wrapping around it what did i tell you chromatin was made up of dna and histone proteins let's take a quick second to understand the significance of this 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 or reddish structure what is that 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 what the heck is an octomer so octomers 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 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 to make an octamer so i'm going to have two of each one of these things and the combination of all of these two four six eight these components the h2a h2b h3h4 they make up an octamer and all of these h's are histones okay they're proteins what i really need you to focus on with this histones have particular amino acids called lysine and arginine and the significance of these is that lysine and arginine are positively charged amino acids very important that you guys remember that okay why 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 it's phosphate groups within the dna that creates a negative charge 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 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 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 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 the reason why is histone proteins in dna can be modified via the process of epigenetics we're not going to get into a lot of detail on that but i want to just quickly brush over this because there is pertinence to this for your usmles so there's concepts of what's called epigenetics where you control or regulate the expression of genes throughout you know the lifetime from parental to daughter cells and and and so on and so forth and how we do this is by we modify the activity of the interaction between dna and histone proteins and how do we do that well one of the things that we can do is we can modify the dna okay and we'll talk about this one 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 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 we're going to put cgcgcg 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 and what these enzymes do is they add methyl groups onto wherever these cytosine and guanine areas are you know what that does whenever you add methyl groups onto these cpg islands 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 rna and then make proteins 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 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 and our liver cell we're going to make a particular protein and 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 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 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 okay right now the histone proteins in the dna are really tightly interacted with one another not a chance and heck a little enzyme can get in there and transcribe the dna there where that histone protein is occupying so what i can do is 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 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 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 that portion of the dna so this can be transcribe so transcription can occur here now let's say i take another situation 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 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 but if instead i add on two to three of these actual histone proteins then what's gonna happen i'm gonna really tighten up the interaction between the dna and the histone proteins there's not a chance and 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 rna proteins so on and so forth 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 okay well i have what's called a a d acetylase and what i did is i had this dsc lace inhibit or remove the acetyl group if i remove the acetyl group what happens am i going to allow for relaxation of the dna and the histone proteins no they're going to be tightly compacted with one another are we going to be able to transcribe that gene and make rna no so in quick summary if i add acetyl groups to the histone proteins what does it do relaxes the dna and histone proteins you relax it can you occur with can gene transcription occur yes i add one methyl group onto the histone protein what does it do it relaxes the histone from the dna can you transcribe it yes i add two to three methyl groups to the histone proteins what does it do it tightens up or condenses the interaction between the dna and the histone proteins can you transcribe it no last thing here is i take a d acetylase enzyme remove off the acetyl group now what's going to happen with the dna and the histone proteins is there going to be a loose interaction no there'll be a tight interaction and what happens transcription is inhibited this is really important i really need you guys to remember this stuff okay that covers our kind of epigenetic aspect of this now let's get back over here one quick thing before we move into the kind of the really small units of dna as there's one more histone protein 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 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 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 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 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 s like the actual microscopic components of these 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 so what is this here component called this is called your sugar phosphate backbone 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 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 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 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 now let's dig into each of these different constituents of dna all right so the next thing i want you guys to know what are the constituents what makes up these nucleotides 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 if i have two rings what's called a heterocyclic ring okay two of them are representing two boxes here this makes up particular types of nitrogenous bases 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 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 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 like there's actually three but we're only talking about this for dna so there's actually technically three pyrimidines i'll put it down but i'm gonna refer to it only an rna this is particular to dna the three types of pyrimidines you can remember by cut pie 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 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 have a hard time separating them cut pie is going to be cytosine uracil thymine that makes it pyrimidines the remaining two are adenine and guanine okay now that's one component we talked about the next component is the pinto sugars the pinto 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 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 that's 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 this is where well it's actually right here but what happens is this is what connects to your nitrogenous base 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 okay on the two carbon this is what really makes the difference in ribose there's an o h and deoxyribose which we'll talk about in a second there is no oh it's just an h 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 o h group on the fourth carbon nothing on the fifth carbon this is where i need you to remember the next structure and that next structure we're going to draw here in orange is going to be where the phosphate group will combine on to okay so that's where the phosphate group is i'm just trying to give you the significance of the ribose sugar so three group o h five group phosphate two group if it's ribose has an o h group first carbon has the nitrogen if it's a deoxyribose it's literally the same dang structure the only thing that's different is what guys i know you guys are yelling it out this is a what 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 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 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 difference between oxy ribose and deoxy is the oh on the second carbon h on the second carbon for deoxyribose the next thing is the phosphate group 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 headstone proteins so what do i need you to know is just this basic structure of phosphate is found on what carbon first thing i need to know is that it's a very negatively charged so that allows for that interaction with dna and histones 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 we're not going to go into crazy detail because they can kind of be confusing we 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 the basic difference if we just take for example i take one nitrogenous base and i take one pinto sugar it doesn't matter that's all a nucleoside is is i'm just going to have this structure here and my phosphate there and then what do i have coming off here let's just say i have a period i have adenine so if i just have what two structures that is what makes up a nucleoside what are the two components a pentose sugar and what else a nitrogenous base it's not technically a nucleoside this is it's not not technically a nucleotide it's actually a nucleoside so nitrogenous base pentose sugar is what's called a nucleoside 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 i have my pentose sugar i have my o-h 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 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 we now have a basic concept of this these do have different names i don't want to get too bogged down into that but i want you to know the difference between a nucleoside no phosphate nucleotide phosphate 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 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 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 is represented as a the other one is going to be my guanine often represented as g the next thing you guys need to know is that adenine and guanine have to have an interaction with some of these pure pyrimidines what are those interactions and that's very important here 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 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 there's what's called hydrogen bonds that link these different 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 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 this particular play with dna replication that's why i'm telling you that 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 bay thing in egs remember that hydrogen bonds are weak bonds 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 uh the hydroxyl group and that's what the one i want to talk about now so let's say that i take my nucleotides what's a nucleotide tester knowledge a phosphate group of pentose sugar in that nitrogenous base i'm going to string them up in a line when you look at dna dna has this concept of what's called a anti-parallel type of arrangement so it has what kind of arrangement here it has an anti parallel arrangement and what that means is that on one end let's say on this left side it's a range from five to three and again you guys know what that means we'll explain it 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 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 and to five end fashion that's the concept of anti-parallel dna so it's moving and it's basically oriented in opposite directions of one another now let's explain this complementarity aspect with this anti-parallel strand 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 wanted to interact with this actual nitrogenous base on the right strand according to complementarity which one of it would 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 with this one have to be according to complementarity adenine 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 and then let's just finish it off for the heck of it here's your cytosine which nucleotide do you think it would have to be to have interaction here according to complementarity guanine right and then for simplicity or to be you know complete how many bonds here one two three one two three one two one two hydrogen bonds the next concept here is this backbone remember i told you that there was 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 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 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 5 and 3n thing but this strong bond is formed between the 5 end of 1 and the 3 end of another nucleotide what's on the five end you guys remember what did we say was on this five end the phosphate group we're just going to represent here's our phosphate group okay what did we say was always on the three end here we'll write it down just for simplicity sake this one is your five end this is your three and what was on the three end again the oh group 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 okay so now what i want to do is is i want to make a bond between each one of these a bond here phosphodiester phosphodiester phosphodiester when you do this you actually get rid of the hydrogen again we're not going to worry too much about that i just want you to know that this sugar phosphate backbone is made up of a phosphodiester bond combining phosphate of five group to the hydroxyl group of the three group of another nucleotide and so this would be our phosphodiester bond 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 depending upon the concept of complementarity 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 now let me take this nucleotide because this is not how um let me take this dna because this is not how dna looks like it does in a perfect world when you're drawing it out but it 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 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 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 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 and this groove is actually the one that i really wanted 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 if i give a drug called dactinomycin ductinomycin dactynomycin kind of sits within that minor groove and what does it do it inhibits the dna from being able to replicate imagine it kind of just sitting there and an enzyme has to kind of jump into this portion to kind of go and replicate the dna it can't because it's being blocked by what thing dactynyl myosin let's pretend that the dectanomycin is this pink structure just kind of sitting in this area here and you want to bring an enzyme down to tran 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 and the last little fun fact 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 this right here is made up of about 10 nucleotide like 10 nucleotides for each turn that you make okay so for each turn 10 nucleotides 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 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 their structure of dna or the organization of dna 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 usn release particularly related to drug induced lupus so with lupus or sle right there's a it's 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 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 destruction of particular cells and injury to a lot of cells 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 or like reaction and you can remember this via the mnemonic ship and it goes sulfonamides hydralazine isoniazid which is commonly abbreviated inh procainamide which is an antiarrhythmic and then an anticonvulsant known as phenytoin 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 and 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 believe it or not huntington's disease can be related to issues with the histone proteins you know how what happens is there's issues where in histone proteins they have some issue with there's an in there's an increase in what's called a diacetylation remember what i said the d acetylation was and there was a reason why i took the time to mention that do you remember what happens when you increase d acetylation you remove acetyl groups 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 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 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 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 so in that situation this can lead to neuron injury and death and you know where this is particularly type of important within the basal ganglia structures with inside of the central nervous system and what happens is there is injury to particular structures within the basal ganglia and that causes a type of abnormal or hyperkinetic movement disorder and this leads to a hyper kinetic movement disorder does that make sense so again simple concept huntington's disease is related to an increase in deacetylation decreasing transcription of growth factors as well as there's a transcriptional dysregulation of the what's called the huntington's protein and abnormal proteins produced and it causes increased neuron injury and death particularly where basal ganglia and the result with hyperkinetic movements okay the last thing that i want us to talk about here is that remember that we talked a lot about purines and pyrimidines and nucleotides and all their significance because they make up dna what if i inhibited the synthesis of these purines these pyrimidines 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 if i gave anti-cancer drugs or i gave drugs to 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 so what would this be antibiotics antivirals and what else it could also be anti-parasitics and also you know what else we use these for immunosuppressants 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 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 another one is called azathioprine another one is called ribavirin and another one is called mycophenolate six mercaptopurine and is are primarily immunosuppressant drugs 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 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 bacterium which is an antibiotic methotrexate is also used as immunosuppressant another one called permethamine okay so there's a bunch of this promethamine is actually an antiparasitic so you can use these different drugs to inhibit the synthesis of pyrimidines as well and the last one is what if i wanted to inhibit 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 hydroxy okay so that gives us the most important clinical significance related to the structure of dna all right engineers in this video today we talk about the structure of dna i hope it made sense and i hope that you guys did enjoy it alright engineers as always until next time [Music] you