Understanding the Structure of DNA: Key Components and Functions
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Introduction
In this comprehensive guide, we will explore the intricate structure of DNA, beginning with its location within the nucleus of the cell. Understanding the components of DNA not only enhances our grasp of biology and genetics but is also crucial for students and professionals alike, particularly those preparing for exams like USMLE. Let’s break down this complex subject into manageable segments.
The Nucleus: Home of DNA
Components of the Nucleus
The nucleus serves as the repository for DNA within eukaryotic cells, offering a protective environment for genetic material. The main components of the nucleus include:
- Nuclear Envelope: A double membrane consisting of an outer and inner membrane, providing a barrier and housing the contents of the nucleus.
- Nuclear Pores: Protein complexes that allow selective transport of molecules between the nucleus and the cytoplasm, crucial for mRNA export and nucleotide import.
- Nucleoplasm: The viscous fluid within the nucleus containing various substances, including nucleotides, enzymes, and the nucleolus, where ribosomal RNA (rRNA) synthesis occurs.
The Structure of DNA
Chromatin: The Form DNA Takes
Inside the nucleus, DNA exists in a complex form known as chromatin, which provides a compact structure necessary for fitting within the confines of the nucleus. Chromatin is composed of:
- Histone Proteins: These proteins play a pivotal role in DNA packaging. They allow DNA to coil and fold, too tight for transcription to occur in dense regions (heterochromatin), ensuring that certain genes remain inactive based on cellular needs.
- Euchromatin: Represents less condensed regions of chromatin that allow gene expression and transcription.
Nucleosomes: The Basic Units of Chromatin
Nucleosomes consist of DNA wrapped around a core of histone proteins and are fundamental in condensing DNA into a manageable form. The interaction includes:
- Histone Octamer: Formed by pairs of histone proteins H2A, H2B, H3, and H4, creating a structural motif that the DNA wraps around.
DNA Composition: Nucleotides and Their Structure
Components of Nucleotides
DNA is constructed from nucleotides, which are the building blocks of the genetic material. Each nucleotide comprises three components:
- Pentose Sugar: Specifically, deoxyribose in DNA, with a structure critical for nucleotide formation.
- Nitrogenous Base: Two types include purines (adenine, guanine) and pyrimidines (thymine, cytosine), with unique pairing rules (A-T and G-C).
- Phosphate Group: This negatively charged group connects nucleotides via phosphodiester bonds, creating a sugar-phosphate backbone essential for DNA stability.
The Double Helix Structure
The DNA molecule forms a double helix, characterized by:
- Antiparallel Strands: One strand runs in the 5’ to 3’ direction while the complementary strand runs in the opposite 3’ to 5’ direction.
- Complementarity: Base pairing occurs through hydrogen bonds, with A pairing with T and G pairing with C, reinforcing the DNA's stability.
Epigenetics and Gene Regulation
Epigenetics refers to heritable changes in gene expression without altering the underlying DNA sequence. Key mechanisms include:
- Histone Modifications: Acetylation and methylation of histones that regulate access to DNA, impacting transcriptional activity.
- DNA Methylation: Particularly at CpG islands where methylation leads to gene silencing, crucial for development and cellular differentiation.
Clinical Relevance
Understanding DNA structure is vital, especially in medical contexts:
- Drug-Induced Lupus: Certain medications can lead to an autoimmune response targeting histones, resulting in disease pathogenesis.
- Cancer Treatment: Many chemotherapeutic agents target DNA synthesis pathways, inhibiting both purine and pyrimidine synthesis to prevent cancer cell proliferation.
Conclusion
Grasping the structure of DNA, including its components, chromatin configuration, and the regulatory mechanisms of gene expression, is fundamental in both biology and medicine. This knowledge not only prepares you for examinations but also provides insight into the molecular underpinnings of genetics and the potential for therapeutic interventions in various diseases.
For additional resources on DNA structure and function, consider visiting our supporting links available in the video description or checking out our Patreon for in-depth materials. Until next time, keep exploring the wonders of biology!
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
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
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
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
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 thing i want you to associate with the outer membrane is where the ribosomes will be because
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
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
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
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
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
which are your proteins and there's different types of subunits there's a large ribosomal subunit and a
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
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
other one is your good old dna now these two combos are what make chromatin but chromatin is also a little
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
where the histones in the dna have such a strong attraction with one another that it's really hard for little enzymes
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
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
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
is the chromatin during cell replication it condenses down into what's called chromosomes
dna a little bit more is looking at how chromosomes a really condensed structure of chromatin contains loops and loops in
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
level okay so once i take my chromosome i'm going to start yanking some of the dna out of this as i
i have my chromosome i yank some of it out and then i get this loopy kind of continuous fiber that
keep getting into the smaller and smaller versions of it as i'm looking deeper into the structure
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
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
have to have double of everything to make an octamer so i'm going to have two of each one of these things
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
has a negative charge so dna has i'll tell you quick it's phosphate groups within the dna
and so because they have all these positive charges around them what happens to opposite charges they
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
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
this because there is pertinence to this for your usmles so there's concepts of what's called
you know the lifetime from parental to daughter cells and and and so on and so forth and how we do
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 what happens is we can use different types of enzymes and what these enzymes do is they add
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
which genes we want to be expressed in particular cells and our liver cell we're going to make a 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
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
and what these enzymes do is they add on what's called an acetyl group okay they can add on an acetyl group and
and makes it really lax okay we'll leave this one alone because we're going to talk about that in a
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
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
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
so remember if i add two to three methyl groups what's going to happen it's going to repress
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
am i going to allow for relaxation of the dna and the histone proteins no they're going to be tightly compacted
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
remove off the acetyl group now what's going to happen with the dna and the histone proteins is there going to be a
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
this is the h1 linker protein so this is actually a linker protein it links the dna nucleosomes between one
protein guess what it has to be the most positively charged histone protein so it has the most
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
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
phosphate backbone and obviously as you can tell it's made up of what's called a ribose sugar
nitrogenous bases that we'll discuss because there's there's a lot of high-yield stuff associated with that
make up a nucleic acid so when someone says what is dna you can just say it's a sequence of
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
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
uracil and this is the only one that is not in dna it's only in rna all these other ones
nitrogenous bases and again two rings purines single ring pyrimidines if you're trying to have a
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
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
this is your number three carbon this is the number four carbon this is the number five carbon it's
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
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
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
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
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
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
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
is what's called a nucleoside now a nucleotide is all of these things so that's where i
i have my pentose sugar i have my o-h on my third carbon we're talking about dna so we need just
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
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
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
very important here adenine loves to interact with thymine and guanine loves to interact with
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
that should tell you that it's probably easier to break the bonds between adenine and thymine than it is to break
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
let's say on this left side it's a range from five to three and again you guys know what that means
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
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
base with this one have to be according to complementarity adenine let's use the next concept let's
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
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
so i want you to remember this is a strong bond and it's formed again i told you we're going to
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
the oh group i'm going to form a bond between these two structures here and when i do that that bond between the
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
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
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
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
when it does that it creates these little grooves if you will this groove right here is a big old
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
minor groove and the minor groove is important because guess what a lot of enzymes which are going to
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
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
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
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
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
that i need you guys to remember is huntington's disease believe it or not huntington's disease can be related to
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
it tightened up the interaction between the histone and the dna if you tighten up the interaction between the histone
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
do is they help to stimulate nerve growth and repair and kind of some of that aspects of it right
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
within the basal ganglia structures with inside of the central nervous system and what happens is there is injury to
kinetic movement disorder does that make sense so again simple concept huntington's disease is
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
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
antivirals and what else it could also be anti-parasitics and also you know what else we use these
causing a lot of havoc on our body that is important and so what we can do is we can give drugs within these
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
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
trimethoprim which is commonly used in what's called bacterium which is an antibiotic methotrexate is also used as
promethamine is actually an antiparasitic so you can use these different drugs to inhibit the synthesis
purine and pyrimidine synthesis there's a bunch of different drugs that can do that as well one of the big ones
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