Full transcript
0:14what's up ninja nerds in this video
0:15today we're going to be talking about
0:16the structure of dna but before we get
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0:33more in this learning process all right
0:35engineers let's get into it
0:37all right ninja nurse when we start
0:38talking about the structure of dna
0:40before we do that we have to have a nice
0:41little conversation about the nucleus
0:43because that's where dna is housed
0:44so let's have a quick little dive into
0:46the structure of the nucleus
0:48what are the components within the
0:49nucleus and what are the basic functions
0:51of what they do
0:52first thing is here here's we see the
0:53nucleus and you have this blue structure
0:56a double membrane kind of structure it's
0:57a phospholipid bilayer if you will
1:00and this phospholipid bilayer is
1:01referred to as your
1:03nuclear envelope and we'll go over all
1:05the different components of that
1:07okay the next thing is within the
1:09nuclear envelope you have these little
1:10proteins
1:12that are nuclear kind of core complex
1:14that allow for
1:15certain things to be able to move to and
1:18from the nucleus and into the cytoplasm
1:20and this structure right here is very
1:22important and these are called your
1:23nuclear
1:24pores okay and they're usually made up
1:27of proteins which help with the
1:29transport of things
1:30to and from the actual cell cytoplasm
1:33and nucleus
1:34the next thing i need you guys to know
1:35is inside
1:37of the actual nucleus is a big component
1:41of
1:41a bunch of stuff and that bunch of stuff
1:43that's inside of it
1:44all the stuff inside is called the
1:48nucleoplasm
1:49and there's a couple different
1:51components to the nucleoplasm
1:53that we're going to go into great detail
1:54in okay and this is the one that we'll
1:56pretty much focus on but again
1:58we have the main components here that we
2:00need to know for the structure of the
2:01nucleus
2:03now first thing nuclear envelope
2:05remember i told you that there's two
2:06components there's an outer membrane and
2:08an inner membrane that's the thing i
2:10need you to know
2:11this outer membrane this component right
2:13here is what's
2:14kind of having ribosomes studded around
2:17the outside
2:18okay so the next thing is your outer
2:20membrane
2:22the thing i want you to associate with
2:24the outer membrane
2:25is where the ribosomes will be because
2:27what will happen is
2:28mrna will come out of these nuclear
2:30pores near the outer membrane
2:32bind with a ribosome and then get
2:34translated to the
2:35rough endoplasmic reticulum and then
2:38that's where translation
2:39protein synthesis will occur the next
2:41thing is the inner membrane
2:43the inner membrane is very important and
2:45there's a particular
2:46pathology that can be involved with the
2:48inner membrane that i want you guys to
2:50know for your usmles
2:52and what is that the inner membrane
2:54contains a very important protein i want
2:56to draw this one out here in pink
2:57because of this pink filamentous protein
2:59that's on the inside
3:00this inner membrane kind of provides a
3:02structural framework for the
3:04actual nucleus and allows for
3:05interaction with chromatin where genes
3:07are expressed
3:08and also undergo replication and this
3:11protein is called
3:12lamins there's lamin proteins and why
3:15you guys need to know this that there's
3:16a mutation within a particular type of
3:19lamin called lamin a
3:21and what happens is if it's absent it
3:23causes individuals patients who
3:26have this disease to age very very
3:28quickly and it's called progeria
3:30okay the next thing is your nuclear
3:33pores your nuclear pores are very
3:34straightforward
3:35what do they do they allow for things to
3:37move out of the nucleus into the
3:39cytoplasm
3:40and from the cytoplasm into the nucleus
3:43what would we need for that just give me
3:45one quick example
3:46of something that would be going out via
3:49the nuclear pores
3:50really quick one mrna mrna would be one
3:53that's kind of
3:54leaving the nucleus
3:57because we need this mrna to
4:00go out into the cytoplasm and get
4:02translated by the ribosomes
4:04all right so give me an example of
4:05something coming in to the nucleus what
4:07do we need to make dna that's a perfect
4:10example
4:10you know you synthesize nucleotides
4:12within different areas of the cell
4:14what if i bring in nucleotides that
4:17could be a very simple reason of why
4:19i need this little transport protein or
4:21nuclear pores to move things
4:23in and out of the nucleus really simple
4:24example right it's meant to be basic
4:27the next thing is the nucleoplasm in the
4:29nucleoplasm there's two primary things
4:31that i want you guys to know
4:33the first one here we're going to color
4:35coordinate is this big circular like
4:37little chex mix looking thing this thing
4:39is called
4:41your nucleolus this is one of the
4:42components of the nucleoplasm
4:45what i want you to know is in the
4:46nucleolus this is where
4:49your r rna synthesis occurs
4:52so you have some dna in the area of the
4:55nucleolus
4:56and what's happening is it is getting
4:58transcribed to making rrna
5:00also you're making some subunits
5:04some ribosomal subunits and the reason
5:06why is
5:07when you make rrna which is a nucleic
5:10acid and you make subunits
5:12which are your proteins and there's
5:13different types of subunits
5:15there's a large ribosomal subunit and a
5:17small ribosomal subunit
5:18the combination of these two is what
5:21gives you
5:22your ribosomes okay and that's what i
5:24want you guys to remember
5:26so what i tell you guys is that in the
5:27nucleolus what is happening there
5:29ribosomal synthesis you know what's
5:31actually really interesting ribosomes
5:33are
5:33just small enough that they can fit
5:36through the nuclear pore
5:37okay and so that also is another thing
5:39that can be shuttled out all right so
5:41the next component of the nucleoplasm
5:43is your chromatin and this is what i
5:45really want us to focus on because this
5:46is where dna is
5:48so chromatin i need you to remember that
5:50this is made up of two different things
5:51that we'll discuss in a little bit more
5:52detail
5:53one is what's called histone proteins
5:57okay these are very important and the
5:59other one is your good old
6:00dna now these two combos are what make
6:04chromatin but chromatin is also a little
6:06bit special
6:07and we'll talk about how but histones
6:09and dna
6:10their combination works in a particular
6:13way
6:14because of their positive negative
6:15attraction that it condenses dna
6:18into really really compact structures
6:20that can fit within a nucleus in
6:22our in our cells dna is really long
6:25and if i can condense it i can fit a
6:27bunch of dna inside of my nuclei
6:30so what happens is chromatin
6:33can get condensed down into two forms
6:36one of the forms is the highly condensed
6:39h highly condensed i want you to
6:41remember heterochromatin
6:44heterochromatin what i want you to
6:46associate this with
6:47highly condensed in other words this is
6:51so condensed
6:52where the histones in the dna have such
6:54a strong attraction with one another
6:56that it's really hard for little enzymes
6:58to get in there transcribe the dna and
7:00make
7:00rna so what would happen with this there
7:03would be
7:04no transcription
7:07in this type of chromatin
7:10very very important very high yield the
7:13next thing is
7:14there's another type of chromatin but
7:16this one is u-chromatin
7:18and remember that e it's expressed
7:22so this is a loose chromatin and i like
7:26to remember
7:26e for expressing what does that mean
7:29it's expressing
7:30it's there's a weak attraction
7:33there's a relaxed kind of relaxed
7:35attraction between the histones
7:37and the dna and because of that there's
7:40nice space where the
7:41dna the rna polymerases can get in there
7:44and make rna
7:45and so this occurs because
7:49we want this portion of the dna to be
7:51able to
7:52undergo transcription so again big
7:55difference between hetero is highly
7:56condensed
7:57does not undergo transcription
7:58euchromatin is loose chromatin or
8:01expressing chromatin
8:03meaning that you can transcribe it and
8:05make rna
8:06get it very important okay
8:10the last thing i want you guys to know
8:11is that chromatin whenever our cells are
8:13undergoing a lot of replication
8:15they want to allow for that chromatin to
8:17get passed on to the daughter cell so
8:19your parent cell has to pass on the
8:21dna to daughter cells and so the way it
8:24does that
8:24is the chromatin during cell replication
8:28it condenses down into
8:31what's called chromosomes
8:35and that is where i want us to kind of
8:37take a quick little second here and
8:39understand
8:40dna a little bit more is looking at how
8:43chromosomes a really condensed structure
8:46of chromatin contains loops and loops in
8:50loops of dna wrapped around histone
8:52proteins and what's the significance of
8:54that
8:54let's move on to that part all right so
8:56we talked about how chromatin is made up
8:57of dna histone proteins
8:59and whenever the cells are starting to
9:00replicate they need to condense their
9:02chromatin down so that they can easily
9:03pass their genetic material onto the
9:05daughter cells so what i want you to
9:07recognize is this right here
9:08is our chromosome and what i want us to
9:11do is i want to yank
9:13all of that chromatin out of the
9:15chromosome
9:16and look at it deeper and deeper to the
9:19microscopic
9:20level okay so once i take my chromosome
9:23i'm going to start
9:24yanking some of the dna out of this as i
9:26yank some of the dna out it kind of
9:28comes out in this loopy kind of
9:30continuous fiber so
9:31i have my chromosome i yank some of it
9:33out and then i get this
9:35loopy kind of continuous fiber that
9:37you're going to see here
9:40after i continue to keep kind of going a
9:42little bit and i
9:43keep getting into the smaller and
9:45smaller versions of it as i'm looking
9:46deeper into the structure
9:48then it starts to get tight helical
9:51fibers
9:53okay so we get tight helical fibers so
9:57we got loopy continuous fibers
9:58tight helical fibers and then what
10:00happens is you can't really see it that
10:01well but they're in there i'm going to
10:03draw some little red
10:04circles and little red dots in there you
10:06start seeing these red structures
10:08that the dna is kind of wrapping around
10:11and that's where we got to zoom in on
10:13them you see this red structure here
10:15where dna is wrapping around it what did
10:17i tell you chromatin was made up of
10:19dna and histone proteins let's take a
10:21quick second to understand the
10:23significance of this
10:24so now we're going to take and zoom in
10:26on this little structure here because
10:28there's a significance that we need to
10:30kind of talk about a little bit
10:31so we know that dna is wrapped around
10:33this kind of big or reddish structure
10:35what is that so here's our dna we're
10:37kind of zooming in on it
10:38and then the next component is this red
10:40structure here and this is a histone
10:43kind of octamer what the heck is an
10:46octomer
10:46so octomers you know there's eight
10:49there's eight of something
10:50and there's particular histone proteins
10:52and i and it's really quick that i want
10:53you guys to know this
10:54there's what's called h2a
10:58h2b h3
11:02and h4 and so if you count these up
11:06right there's four of these so what do i
11:08have to have double of everything
11:10to make an octamer so i'm going to have
11:12two of each one of these things
11:14and the combination of all of these two
11:16four six eight
11:18these components the h2a h2b h3h4
11:21they make up an octamer and all of these
11:24h's
11:24are histones okay they're proteins what
11:28i really need you to focus on with this
11:30histones have particular amino acids
11:34called lysine and arginine
11:40and the significance of these is that
11:42lysine and arginine
11:43are positively charged amino acids
11:47very important that you guys remember
11:48that okay
11:50why because dna and we'll talk about
11:52what is
11:53making dna negative a little bit later
11:55but dna
11:56has a negative charge so dna has i'll
12:00tell you quick
12:00it's phosphate groups within the dna
12:02that creates a negative charge
12:04so these histone proteins they all have
12:06positive charges
12:08and so because they have all these
12:10positive charges around them
12:11what happens to opposite charges they
12:14attract one another
12:15so then the lysine and arginine on the
12:17histones will interact with the
12:18phosphate groups on dna and tightly
12:20compact with one another
12:21and that's what allows the dna to get
12:23really nice and condensed
12:25that is why i really need you guys to
12:26know that there's a particular name
12:30for whenever the dna wraps twice around
12:33this
12:33octamer of histone proteins you know
12:35what this is called we call this a
12:37nucleosome
12:38so we call this a nucleosome
12:42why am i spending some time mentioning
12:44the significance of the nucleosome
12:46and these histone proteins i'll tell you
12:48why the reason why is
12:51histone proteins in dna can be modified
12:54via the process of epigenetics we're not
12:55going to get into a lot of detail on
12:56that
12:57but i want to just quickly brush over
12:59this because there is pertinence to this
13:00for your usmles
13:01so there's concepts of what's called
13:03epigenetics where you control or
13:06regulate the expression of genes
13:08throughout
13:09you know the lifetime from parental to
13:11daughter cells and
13:12and and so on and so forth and how we do
13:15this
13:16is by we modify the activity of the
13:19interaction between dna and histone
13:21proteins
13:21and how do we do that well one of the
13:23things that we can do is we can modify
13:25the dna okay and we'll talk about this
13:28one
13:29and the next thing that we can do is
13:31besides modifying dna
13:32is we can modify histone proteins and
13:35this is the one that's a little bit more
13:37significant
13:39with modifying dna within dna there's a
13:42specific thing that you can do let's say
13:44here i have a quick
13:45strand of dna and in the dna there's
13:48particular nucleotides called cytosine
13:50and guanine
13:52these are located in these areas here
13:54we're going to put cgcgcg
13:58these areas where there's a lot of
13:59cytosine and guanine are called cpg
14:01islands
14:02and what happens is we can use different
14:04types of enzymes
14:06and what these enzymes do is they add
14:09methyl groups
14:10onto wherever these cytosine and guanine
14:13areas are
14:14you know what that does whenever you add
14:15methyl groups onto these cpg
14:17islands it basically
14:20inhibits this area of dna from being
14:23able to
14:24be expressed if you can't express a
14:26particular part of dna can you
14:28transcribe it
14:29make rna and then make proteins no
14:32that is important so what i want you to
14:34remember is epigenetically
14:35we can modify the dna by methylating
14:38what's called what are these little
14:40things here called we call them
14:42cpg islands areas of
14:45lots of cytosine and guanine we
14:47methylate them and what is the response
14:49to this
14:51this inhibits gene
14:56transcription very important so that's
14:59one way that we can control
15:00which genes we want to be expressed in
15:02particular cells and our liver cell
15:04we're going to make a particular protein
15:06and the other cell like in our brain we
15:07might not want to make that particular
15:09protein
15:10if we methylate that gene that's what
15:11determines the differences
15:13pretty makes sense right same thing with
15:16the histone proteins
15:18if we take for example those histone
15:19proteins and we actually kind of wrap
15:21some dna around it
15:23here i'm going to have a histone
15:24proteins like this
15:26dna here and then inside of this is
15:28going to be your histone proteins
15:30okay right now the histone proteins in
15:33the dna are really tightly interacted
15:35with one another
15:36not a chance and heck a little enzyme
15:39can get
15:40in there and transcribe the dna there
15:42where that
15:43histone protein is occupying so
15:46what i can do is is i can use special
15:49little enzymes
15:51and what these enzymes do is they add on
15:54what's called an acetyl group
15:56okay they can add on an acetyl group and
15:59when i add on the acetyl group it does
16:01something very very interesting what
16:03does it do
16:03let me show you it takes this
16:06interaction between the dna and the
16:07histone proteins
16:09and makes it really lax
16:12okay we'll leave this one alone because
16:14we're going to talk about that in a
16:14second but
16:15now look the histone protein between the
16:19dna there's a lot more space
16:21if there's a lot of space now what can
16:24happen
16:26i can now have my little rna polymerase
16:28enzyme get in there
16:29and transcribe that portion of the dna
16:32so this can be transcribe so
16:36transcription can occur here
16:42now let's say i take another situation
16:45where instead i'm going to
16:48put a methyl group on that histone
16:50protein okay
16:51so now what i'm going to do is i'm going
16:52to put a methyl group onto that histone
16:54protein
16:55now here's the thing that's interesting
16:58if i only add in one methyl group
17:02just one methyl group okay we'll put
17:05that here
17:06it can perform the same type of effect
17:09as acetylation just one so what i'm
17:12going to do is i'm just going to put
17:13one methyl group here it can perform the
17:16same type of action as
17:18acetylation where it can relax the
17:20interaction between the dna and the
17:22histone proteins
17:23allowing for transcription but
17:26if instead i add on
17:30two to three of these actual histone
17:33proteins then what's gonna happen
17:36i'm gonna really tighten up the
17:38interaction between
17:40the dna and the histone proteins there's
17:42not a chance and heck
17:44that the rna polymerase can get in there
17:47and transcribe the dna
17:48so remember if i add two to three
17:51methyl groups what's going to happen
17:54it's going to repress
17:55gene transcription inhibit the gene from
17:58being
17:58transcribed making rna proteins so on
18:02and so forth
18:02so the result of this is you inhibit
18:08transcription the last thing i want to
18:11mention here
18:12is that you can get the same kind of
18:15effect
18:16with this high amounts of methyl groups
18:18that you're adding on if what if i just
18:20took and i used a particular enzyme okay
18:23well i have what's called a
18:24a d acetylase
18:30and what i did is i had this dsc lace
18:33inhibit or remove
18:34the acetyl group if i remove the acetyl
18:37group what happens
18:38am i going to allow for relaxation of
18:40the dna and the histone proteins
18:42no they're going to be tightly compacted
18:44with one another
18:45are we going to be able to transcribe
18:46that gene and make rna no
18:48so in quick summary if i add acetyl
18:51groups to the histone proteins what does
18:52it do
18:53relaxes the dna and histone proteins you
18:55relax it can you occur with
18:56can gene transcription occur yes
18:59i add one methyl group onto the histone
19:01protein what does it do
19:03it relaxes the histone from the dna can
19:05you transcribe it
19:06yes i add two to three methyl groups to
19:09the histone proteins
19:10what does it do it tightens up or
19:13condenses
19:14the interaction between the dna and the
19:16histone proteins can you transcribe it
19:18no last thing here is i take a d
19:20acetylase enzyme
19:22remove off the acetyl group now what's
19:25going to happen with the dna and the
19:26histone proteins is there going to be a
19:28loose interaction
19:28no there'll be a tight interaction and
19:31what happens
19:32transcription is inhibited this is
19:33really important i really need you guys
19:35to remember this stuff okay
19:37that covers our kind of epigenetic
19:38aspect of this now let's get back over
19:40here one quick thing before we move into
19:42the
19:43kind of the really small units of dna as
19:46there's one more histone protein you're
19:47like dang it
19:48another one you see this brown one here
19:51this brown histone protein is actually
19:53probably one of the most important
19:54histone proteins
19:56and this brown one is called h1
20:00this is the h1 linker protein so this is
20:02actually a linker protein
20:04it links the dna nucleosomes between one
20:08another
20:08you see how it's doing that here's one
20:10linking this nucleosome to this
20:11nucleosome
20:12this one to this one so it's a linker
20:14protein and because it's a linker
20:16protein guess what
20:17it has to be the most positively charged
20:20histone protein so it has the most
20:23positive
20:24charge associated with it so that it can
20:26really condense down
20:28the chromatin that's very important okay
20:31now let's keep going down we've hit our
20:33nucleosomes hard
20:34and we've discussed how we see two wraps
20:36of dna around the histone proteins
20:38as we start really kind of zooming into
20:40the dna around the histone proteins what
20:42do we start getting
20:43we start getting this kind of double
20:45helix structure
20:46and in this double helix structure as we
20:48keep going down and down and down
20:50we really start getting into the s like
20:52the actual
20:53microscopic components of these and what
20:56are these components and this is what we
20:57have to focus on which is very important
20:59one is this kind of backbone here you
21:01see this backbone that i'm shading in
21:03blue
21:04this is called your sugar phosphate
21:06backbone so what is this here component
21:08called
21:09this is called your sugar
21:12phosphate backbone and obviously as you
21:15can tell it's made up of what's called a
21:16ribose sugar
21:17and a phosphate group and then the other
21:20component is these little colorful
21:22things inside
21:24and these are called your nitrogenous
21:27bases
21:28and there's different types of
21:29nitrogenous bases that we'll discuss
21:32because there's there's a lot of
21:33high-yield stuff associated with that
21:35but the combination
21:37of your sugar phosphate backbone and
21:39your nitrogenous bases
21:40are what makes up what's called a
21:43nucleotide
21:44and then a bunch of nucleotides together
21:48make up a nucleic acid so when someone
21:51says what is dna
21:53you can just say it's a sequence of
21:56nucleotides
21:57that are made up of sugar phosphate and
22:00nitrogenous bases
22:01now let's dig into each of these
22:03different constituents of dna
22:05all right so the next thing i want you
22:06guys to know what are the constituents
22:08what makes up these nucleotides and this
22:10is actually kind of the easiest
22:12part thank goodness right you're like oh
22:14i needed this
22:16so here's what i want you guys to
22:17remember easy
22:19simple stuff if i have two rings what's
22:22called a heterocyclic ring
22:24okay two of them are representing two
22:26boxes here
22:27this makes up particular types of
22:29nitrogenous bases
22:31and these are referred to as your
22:33purines
22:34and there's two different types of
22:36purines here one
22:38is referred to as adenine
22:41and the other one is referred to as
22:45guanine
22:49so that's the first thing i need you
22:51guys to know so
22:52two rings for these nitrogenous bases
22:54two heterocyclic rings makes up what's
22:56called your purines
22:57and that's made up of adenine and
22:58guanine the next thing is the red one
23:01the red one if you just have one ring a
23:04single ring structure
23:06this makes up what's called pyrimidines
23:09and your pyrimidines are made up of like
23:12there's actually three
23:13but we're only talking about this for
23:15dna so there's actually technically
23:17three pyrimidines i'll put it down but
23:18i'm gonna
23:19refer to it only an rna this is
23:21particular to dna
23:23the three types of pyrimidines you can
23:24remember by cut
23:26pie cut pie pyrimidines
23:29remember cytosine
23:33uracil and this is the only one that is
23:36not in dna
23:37it's only in rna all these other ones
23:39are going to be in dna
23:41and then thymine
23:44okay these are going to be your
23:46nitrogenous bases
23:47and again two rings purines single ring
23:50pyrimidines if you're trying to have a
23:51hard time
23:52separating them cut pie is going to be
23:55cytosine
23:55uracil thymine that makes it pyrimidines
23:58the remaining two are adenine and
23:59guanine
24:00okay now that's one component we talked
24:04about the next component is the pinto
24:06sugars
24:07the pinto sugars i want you to remember
24:09that this is a a ring sugar
24:11and usually it's in the form of what's
24:12called two different types one is you
24:14have what's called
24:15a oxyribose but we're just going to put
24:17it as ribose and the other one is called
24:20deoxyribose and believe it or not
24:23there's not much of a difference between
24:24these
24:25it's really one just atom that's
24:27different
24:28and what happens is you have this
24:31structure here
24:33that's giving you the basic structure
24:35this is your basic structure here
24:37at this point here this is your number
24:39one kind of carbon here
24:41and what happens is this is where well
24:43it's actually right
24:44here but what happens is this is what
24:47connects to your
24:48nitrogenous base this is your number two
24:51carbon
24:52this is your number three carbon this is
24:54the number four carbon
24:55this is the number five carbon it's
24:57actually very important for you to
24:59remember
24:59primarily three and five
25:02okay on the two carbon this is what
25:06really makes the difference
25:07in ribose there's an o h
25:10and deoxyribose which we'll talk about
25:12in a second there is no oh
25:13it's just an h the next thing i need you
25:16guys to remember here
25:17is on the three carbon every three
25:19carbon whether it be
25:20ribose or deoxyribose there's an o h
25:23group
25:24on the fourth carbon nothing on the
25:26fifth carbon this is where i need you to
25:28remember the next structure
25:29and that next structure we're going to
25:30draw here in orange is going to be where
25:32the phosphate group will combine on to
25:35okay so that's where the phosphate group
25:36is i'm just trying to give you the
25:37significance of the ribose sugar
25:40so three group o h five group phosphate
25:43two group if it's ribose has an o h
25:45group first carbon
25:46has the nitrogen if it's a deoxyribose
25:50it's literally the same dang structure
25:52the only thing that's different is what
25:55guys
25:56i know you guys are yelling it out this
25:57is a what
25:59h there's no oh there
26:03okay that's why it's oxy versus deoxy
26:06right pretty straightforward on the
26:08third carbon what's here oh
26:10on the fourth carbon nothing ch2 which
26:13is your fifth carbon what comes off of
26:15that fifth carbon
26:16you guys remember it is the phosphate
26:19group
26:20which is connected with the fifth carbon
26:22okay so this is going to be
26:24our ribose sugars or our pentose pentose
26:27meaning it's a five
26:28carbon sugar the main things i need you
26:30to remember five carbon has
26:31phosphate three carbon has oh group
26:34difference between oxy ribose and deoxy
26:36is the oh on the second carbon
26:38h on the second carbon for deoxyribose
26:41the next thing is the phosphate group
26:44the phosphate group is really where we
26:45really need to remember that this is
26:46where it's the
26:47negatively charged structure okay so
26:49here's our phosphate group
26:52okay now phosphates
26:55are important because of that negative
26:57charge because that's what allows for
26:59the dna the negative charge of dna to
27:00interact with headstone proteins
27:02so what do i need you to know is just
27:03this basic structure of phosphate
27:05is found on what carbon first thing i
27:07need to know is that it's a very
27:08negatively charged
27:10so that allows for that interaction with
27:11dna and histones and the second thing is
27:14it binds
27:16to what carbon the fifth carbon
27:19on the pentose sugar can't stress that
27:21enough
27:23all right the next thing i need you guys
27:24to know is there's a couple nomenclature
27:27terms that i want you guys to know
27:28we're not going to go into crazy detail
27:30because they can kind of be confusing we
27:31talk about them more in the purine and
27:33pyrimidine synthesis
27:34pathways but i want you to know the
27:35difference between a nucleoside
27:38and a nucleotide the basic difference
27:42if we just take for example i take one
27:44nitrogenous base and i take one pinto
27:47sugar it doesn't matter
27:48that's all a nucleoside is is i'm just
27:51going to have
27:53this structure here
27:59and my phosphate there and then what do
28:01i have coming off here let's just say i
28:02have
28:03a period i have adenine so if i just
28:06have what two structures
28:08that is what makes up a nucleoside what
28:09are the two components a pentose
28:14sugar and what else a nitrogenous base
28:19it's not technically a nucleoside this
28:21is it's not not technically a nucleotide
28:23it's actually a
28:24nucleoside so nitrogenous base pentose
28:27sugar
28:28is what's called a nucleoside now a
28:31nucleotide
28:33is all of these things so that's where i
28:35want us to finish up
28:37a nucleotide is now let's build this
28:38whole thing up here
28:40i have my pentose sugar i have my o-h on
28:43my third carbon
28:44we're talking about dna so we need just
28:46a deoxyribose
28:48my one carbon let's just put here again
28:50adenine or guanine
28:51i'm putting a purine ring
28:54and then again what do i have coming off
28:56here on my fifth carbon
28:59i have that phosphate group
29:03if i have all of these things
29:06what components a phosphate group a
29:09pentose sugar
29:10and a nitrogenous base this is what
29:12makes up a nucleotide
29:14we now have a basic concept of this
29:17these do have different
29:18names i don't want to get too bogged
29:20down into that but i want you to know
29:22the difference between a nucleoside
29:23no phosphate nucleotide phosphate simple
29:26as that
29:27now that we know that let's take a bunch
29:29of nucleotides
29:30string them together and start making
29:32our dna so now what i need us to start
29:35talking about here is
29:36kind of taking these nucleotides
29:37stringing them up together
29:39interacting with one another and making
29:41our dna that's what we know that
29:42nucleotides make up nucleic acids and
29:44dna is one of them
29:45before we do that we have to have a
29:47quick little discussion on the concept
29:49of complementarity
29:50and this is honestly it's like a super
29:52easy thing
29:54let's say i take for example my purines
29:56and i draw these out here my purines i'm
29:57going to have
29:58my adenine which i'm just going to
29:59represent often is represented as a
30:02the other one is going to be my guanine
30:04often represented as
30:05g the next thing you guys need to know
30:08is that
30:09adenine and guanine have to have an
30:12interaction
30:13with some of these pure pyrimidines
30:16what are those interactions and that's
30:18very important here
30:19adenine loves to interact with thymine
30:23and guanine loves to interact with
30:26cytosine
30:27but there's a very significant thing
30:28that i want you guys to remember
30:30these interactions is the basis of your
30:32complementarity these are going to
30:33interact with one another
30:34and the way that they interact with one
30:36another is actually very important
30:38we're going to do it here represented in
30:40blue
30:41there's what's called hydrogen bonds
30:44that link
30:46these different nitrogenous bases
30:48together between
30:49guanine and cytosine and adenine and
30:52thymine
30:53and these hydrogen bonds that i need you
30:54guys to remember is that for adenine and
30:57thymine
30:57there is two hydrogen bonds so what
31:00should that tell you a little bit
31:02that should tell you that it's probably
31:03easier to break the bonds between
31:05adenine and thymine than it is to break
31:06the bond between
31:07guanine and cytosine that comes into
31:09this particular play with dna
31:11replication that's why i'm telling you
31:12that
31:13the next thing is here we have three
31:16hydrogen bonds
31:17so a little bit more difficult to break
31:20the bond
31:21between guanine and cytosine but the bay
31:23thing in egs remember that hydrogen
31:24bonds
31:25are weak bonds they're kind of these
31:27electrostatic interactions
31:29but again these are weak bonds
31:32you know what's a really strong bond
31:35another type of bond between the
31:37phosphates and the uh the hydroxyl group
31:39and that's what the one i want to talk
31:41about now
31:42so let's say that i take my nucleotides
31:44what's a nucleotide tester knowledge
31:46a phosphate group of pentose sugar in
31:48that nitrogenous base i'm going to
31:50string them up in a line
31:52when you look at dna dna has this
31:54concept of what's called a
31:56anti-parallel type of arrangement so it
31:58has what kind of arrangement here
32:00it has an anti
32:03parallel
32:06arrangement and what that means is that
32:08on one end
32:10let's say on this left side it's a range
32:13from five to three
32:17and again you guys know what that means
32:19we'll explain it a little bit in a
32:20second
32:21that means that the right aspect in this
32:23case let's say this is the left
32:25part of the dna the right part of the
32:26dna on this right side it has to be
32:29arranged in the opposite direction going
32:30from top to bottom
32:32which means it has to be arranged in a
32:34three and
32:35to five end fashion that's the concept
32:38of anti-parallel dna
32:40so it's moving and it's basically
32:42oriented in
32:43opposite directions of one another now
32:46let's explain this complementarity
32:48aspect with this anti-parallel strand
32:51let's pretend that this pink structure
32:53here this is a nitrogenous base let's
32:54say that this is
32:55adenine on this left strand we wanted to
32:58interact with this
33:00actual nitrogenous base on the right
33:01strand according to complementarity
33:03which one of it would have to be
33:05it would have to be thymine same concept
33:08here let's say that this one is
33:10which one let's say that this one is
33:12thymine
33:13which nucleotide or which nitrogenous
33:15base with this one have to be according
33:16to complementarity
33:17adenine let's use the next concept let's
33:20say that this pink one here is
33:21guanine which nucleotide do you think it
33:24would have to be
33:25according to complementarity cytosine
33:27and then let's just finish it off for
33:29the heck of it
33:29here's your cytosine which nucleotide do
33:31you think it would have to be
33:32to have interaction here according to
33:34complementarity guanine
33:36right and then for simplicity or to be
33:39you know complete
33:39how many bonds here one two three one
33:42two three
33:43one two one two hydrogen bonds
33:47the next concept here is this backbone
33:49remember i told you that there was
33:50called a sugar
33:51phosphate backbone that's the next thing
33:53i need you guys to know here's what's
33:54called a sugar
33:57phosphate backbone
34:01this sugar phosphate backbone is
34:03important because it's made up of a
34:05particular bond
34:06called a phosphodiester
34:10bond and this is a very very powerful
34:13bond
34:13a very very strong bond covalent bond if
34:17you will
34:18so i want you to remember this is a
34:19strong bond and it's
34:21formed again i told you we're going to
34:23come back to this 5
34:24and 3n thing but this strong bond is
34:27formed between
34:28the 5 end of 1 and the 3 end of another
34:32nucleotide what's on the five end you
34:34guys remember
34:35what did we say was on this five end the
34:37phosphate group we're just going to
34:38represent here's our phosphate group
34:40okay what did we say was always on the
34:42three end here we'll write it down just
34:44for simplicity sake
34:45this one is your five end this is your
34:47three and what was on the three end
34:49again
34:49the oh group i'm going to form a bond
34:52between these two structures here
34:55and when i do that that bond between the
34:58five end
34:59and the three end of one nucleotide is
35:01what makes a
35:02phosphodiester bond a very strong bond
35:05okay
35:06so now what i want to do is is i want to
35:09make a bond between each one of these
35:10a bond here phosphodiester
35:13phosphodiester phosphodiester
35:14when you do this you actually get rid of
35:16the hydrogen again we're not going to
35:17worry too much about that
35:18i just want you to know that this sugar
35:20phosphate backbone is made up of a
35:22phosphodiester bond combining phosphate
35:23of five group to the hydroxyl group of
35:25the three group
35:27of another nucleotide and so this would
35:29be our phosphodiester bond
35:31isn't that cool now that kind of gives
35:35us the basic
35:36concept here of what dna looks like
35:39sequence of nucleotides held together by
35:42phosphodiester bonds
35:44interacting anti-parallel fashion via
35:48hydrogen bonds depending upon the
35:50concept of complementarity
35:52and one strand is moving from five to
35:54three this would be your five end
35:56that would be your three end and the
35:57other one is moving in the opposite
35:59direction
36:00being a three end to five end for that
36:03anti-parallel fashion
36:05now let me take this nucleotide because
36:07this is not how
36:08um let me take this dna because this is
36:11not how dna looks like it does in a
36:12perfect world
36:13when you're drawing it out but it
36:14actually kind of has a three-dimensional
36:16shape where it starts kind of looping
36:17and looping and looping
36:18creating this double helix if you will
36:21so now here we have the dna right
36:23and the dna is in this form of a double
36:25helix and there's a couple things
36:27there's
36:27actually multiple different types of dna
36:29not a chance we're going to talk about
36:30that because it can be kind of
36:31complicated and it's not worth it
36:33so double helix is this kind of
36:35anti-parallel fashion but in a
36:36three-dimensional shape
36:38where you see the dna kind of winding
36:40around in this way
36:41when it does that it creates these
36:43little grooves if you will
36:45this groove right here is a big old
36:47groove and this groove right here that i
36:49want you to know
36:50is called the major
36:53okay it's called the major groove it's
36:55just kind of the anatomy and the
36:56topology of dna
36:58then you have another groove but this
37:01groove is a little bit tinier because of
37:03the way that the dna folds
37:05and this groove is actually the one that
37:07i really wanted to know about which is
37:08called the
37:09minor groove and the minor groove is
37:12important because guess what
37:14a lot of enzymes which are going to
37:16replicate dna
37:17or transcribe some of the dna
37:19particularly replicate the dna bind onto
37:21this portion here
37:22if i give a drug called dactinomycin
37:27ductinomycin dactynomycin kind of sits
37:30within that minor groove
37:32and what does it do it inhibits
37:35the dna from being able to replicate
37:37imagine it kind of just
37:38sitting there and an enzyme has to kind
37:41of jump into this portion to kind of go
37:42and replicate the dna
37:43it can't because it's being blocked by
37:45what thing dactynyl myosin let's pretend
37:47that the dectanomycin is this pink
37:48structure
37:49just kind of sitting in this area here
37:51and you want to bring an enzyme down to
37:53tran
37:54to replicate this dna strand but you
37:56can't because this is blocking it
37:58so that's one of the significances that
37:59i need you guys to remember with respect
38:01to the kind of topology of dna
38:03and the last little fun fact i'll give
38:05you guys is that you see this whole
38:07portion here
38:08of the dna before it makes this kind of
38:09turn to go into another little portion
38:12this right here is made up of about 10
38:14nucleotide
38:15like 10 nucleotides for each
38:19turn that you make okay so for each turn
38:2210 nucleotides then another turn
38:2410 nucleotides okay so again this
38:27really gives us a lot of detail on our
38:29dna structure
38:30a lot of the interactions let's take a
38:32quick little second to appreciate how
38:35if there's any kind of pathology or
38:37certain drugs that we can use
38:39that can alter their structure of dna or
38:42the organization of dna let's talk about
38:44that quick
38:44all right so why did i kind of talk
38:46about all this stuff and really focus on
38:47those histone proteins really
38:48significantly there was a reason why
38:50there's a clinical relevance related to
38:52it that you guys can see on your usn
38:53release
38:54particularly related to drug induced
38:55lupus so with
38:57lupus or sle right there's
39:01a it's kind of a sub type of it what
39:03happens
39:04is in these individuals their immune
39:06system
39:07right their immune system their plasma
39:09cells generate
39:10antibodies and these antibodies
39:14they target particular things you know
39:16what they target
39:17they love to target those histone
39:19proteins
39:21and whenever they target these histone
39:23proteins it leads to a lot of kind of
39:25destruction of particular cells and
39:27injury to a lot of cells
39:29and that is why it's really important so
39:32whenever somebody has drug induced lupus
39:33i guess the first question that you
39:34should have is
39:35what are the drugs that can precipitate
39:37this type of you know autoimmune or like
39:39reaction
39:40and you can remember this via the
39:42mnemonic ship
39:46and it goes sulfonamides
39:50hydralazine
39:55isoniazid which is commonly abbreviated
39:56inh
39:58procainamide which is an antiarrhythmic
40:04and then an anticonvulsant known as
40:06phenytoin
40:07these drugs can sometimes trigger an
40:10autoimmune reaction
40:11so when you're testing for drug-induced
40:13lupus it's different from when you're
40:14testing for sle even though this is kind
40:16of a type of sle
40:17in sle you test for anti-double-stranded
40:19dna anti-smith dna
40:21and drug-induced lupus you're actually
40:22testing for
40:26anti-histone
40:28antibodies okay so that is important
40:32to remember the next particular thing
40:34that i need you guys to remember is
40:35huntington's disease believe it or not
40:37huntington's disease can be related to
40:40issues with
40:41the histone proteins you know how what
40:44happens is
40:46there's issues where in histone proteins
40:48they have some issue
40:50with there's an in there's an increase
40:52in what's called
40:53a diacetylation remember what i said the
40:56d acetylation was and there was a reason
40:59why i took the time to mention that
41:01do you remember what happens when you
41:02increase d acetylation you remove acetyl
41:04groups
41:06if you remove acetyl groups from the
41:08histone proteins what did that do
41:10it tightened up the interaction between
41:12the histone and the dna if you tighten
41:13up the interaction between the histone
41:14and dna can you transcribe it
41:16no what does that result in it inhibits
41:19transcription
41:20so it's going to inhibit or decrease
41:23transcription
41:24you know why that is actually important
41:26there's a couple reasons why
41:28one is in nerves okay particularly
41:30nerves that are involved in our basal
41:32ganglia
41:33they need to release they need to
41:35transcribe particular proteins
41:37called growth factors nerve growth
41:39factors
41:40because what these nerve growth factors
41:42do is they help to stimulate nerve
41:44growth and repair and kind of some of
41:45that aspects of it right
41:47if i have some type of issue where i'm
41:49decreasing the transcription of growth
41:51factors
41:52that are helping with nerve growth
41:54what's going to happen i can lead to
41:56destruction of these nerves over time
41:57because they're not going to have the
41:58proper stimulus to continue to grow
42:00so in that situation this can lead to
42:04neuron injury
42:08and death and you know where this is
42:10particularly type of important
42:12within the basal ganglia structures with
42:15inside of the central nervous system
42:18and what happens is there is injury to
42:20particular structures
42:21within the basal ganglia and that causes
42:24a
42:24type of abnormal or hyperkinetic
42:28movement disorder
42:29and this leads to a hyper
42:32kinetic movement
42:38disorder does that make sense so again
42:41simple concept huntington's disease is
42:44related to
42:44an increase in deacetylation decreasing
42:46transcription of growth factors as well
42:48as there's a
42:49transcriptional dysregulation of the
42:51what's called the huntington's protein
42:52and abnormal proteins produced
42:54and it causes increased neuron injury
42:56and death particularly where basal
42:58ganglia
42:59and the result with hyperkinetic
43:00movements
43:02okay the last thing that i want us to
43:03talk about here
43:05is that remember that we talked a lot
43:07about purines and pyrimidines and
43:09nucleotides and all their significance
43:11because they make up dna
43:13what if i inhibited the synthesis
43:16of these purines these pyrimidines would
43:19i be able to make dna
43:21no so there's drugs that i really want
43:24you guys to remember
43:25like anti-cancer drugs wouldn't that be
43:28a perfect reason why you
43:30definitely would want to like not allow
43:31for dna to replicate as a cancer cell
43:34if i gave anti-cancer drugs or i gave
43:37drugs to
43:38individuals who have an infection and i
43:41actually inhibit the replication of
43:43bacteria
43:44i inhibit the replication of viruses i
43:45inhibit the replication of
43:47parasites so what would this be
43:50antibiotics
43:52antivirals and what else
43:56it could also be anti-parasitics
44:00and also you know what else we use these
44:02for immunosuppressants
44:05inhibiting the replication of
44:08those immune system cells that are
44:10causing a lot of havoc on our body
44:12that is important and so what we can do
44:14is we can give drugs within these
44:16categories
44:16that can inhibit purine synthesis
44:20to give you a couple i don't want to
44:22spend a ton of time on these but a lot
44:24of these are utilized
44:25for example uh some that you may want to
44:27consider here in these situations would
44:29be like what's called
44:30six mercaptopurine another one is called
44:34azathioprine
44:37another one is called ribavirin
44:42and another one is called mycophenolate
44:47six mercaptopurine and is
44:51are primarily immunosuppressant drugs
44:53ribavirin is an antiviral
44:55these would be things that would inhibit
44:57purine synthesis what if i wanted to
44:58give a drug that inhibited
45:01pyrimidine synthesis so i didn't want to
45:04make any of those pyrimidines
45:06what kind of drugs would i give here
45:08this would be things like
45:09methotrexate this would be things like
45:12what's called
45:13trimethoprim which is commonly used in
45:15what's called bacterium which is an
45:16antibiotic methotrexate is also used as
45:18immunosuppressant
45:20another one called permethamine
45:26okay so there's a bunch of this
45:27promethamine is actually an
45:28antiparasitic so you can use these
45:29different drugs to inhibit the synthesis
45:31of pyrimidines as well
45:33and the last one is what if i wanted to
45:34inhibit both of them
45:36purine and pyrimidine synthesis
45:39there's a bunch of different drugs that
45:41can do that as well one of the big ones
45:42that you guys want to remember here
45:44is hydroxy
45:48okay so that gives us the most important
45:51clinical significance related to the
45:52structure of dna
45:54all right engineers in this video today
45:55we talk about the structure of dna i
45:57hope it made sense and i hope that you
45:59guys did enjoy it alright engineers as
46:01always until next time
46:15[Music]
46:22you