Understanding the Structure of DNA: Key Components and Functions

what's up ninja nerds in this video today we're going to be talking about the structure of dna but before we get

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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