DNA Structure and Replication: Crash Course Biology #10

Summary

This script delves into the wonder of DNA, the most intricate and vital molecule, storing genetic instructions for life. It explains DNA's structure, including its double helix form, composed of nucleotides with sugar, phosphate, and nitrogenous bases. Highlighting the discovery of DNA and its replication process, the script also touches on the contributions of scientists like Rosalind Franklin and the importance of enzymes in DNA synthesis and repair, emphasizing DNA's role in defining every living being.

Takeaways

• 🌟 DNA is a double helix structure, considered one of the most complex and important molecules in existence.
• 🧬 Deoxyribonucleic acid (DNA) stores genetic instructions for all cellular activities and is composed of a 6-billion letter code.
• 🔬 DNA was not fully understood in terms of structure until about 60 years ago, highlighting its complexity and the long journey to comprehend it.
• 📏 The DNA from a single cell, if stretched out, would be taller than a human, and the DNA from the body could reach the sun 600 times.
• 🧬🧬 DNA is made up of two polynucleotide chains that are held together by hydrogen bonds between specific nitrogenous bases: adenine (A) with thymine (T), and guanine (G) with cytosine (C).
• 💠 Each DNA molecule consists of nucleotides, which include a five-carbon sugar (deoxyribose), a phosphate group, and one of four nitrogenous bases.
• 🔄 DNA replication is a precise process that ensures every new cell receives an exact copy of the DNA, involving enzymes like Helicase and DNA Polymerase.
• 🔬👤 The discovery and understanding of DNA's structure involved many scientists, including Rosalind Franklin, whose work was critical but not widely recognized.
• 📚 The DNA sequence is so vast that if printed, it would fill about 10,000 books, each 1,000 pages long.
• 🔍 DNA has a proofreading mechanism to correct errors during replication, which is crucial given the vast amount of DNA in the human body.
• 🕊️ RNA, a cousin of DNA, differs in that it is single-stranded, uses ribose instead of deoxyribose, and contains uracil instead of thymine.

Q & A

What is DNA and why is it considered important?

DNA, or deoxyribonucleic acid, is a nucleic acid that contains the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses. It is a molecule composed of two chains that coil around each other to form a double helix, and it is considered important because it carries the genetic information necessary for life.

How long ago was the structure of DNA discovered?

The structure of DNA was not definitively known until about 60 years ago, as mentioned in the script.

What are the four nitrogenous bases found in DNA?

The four nitrogenous bases found in DNA are adenine (A), thymine (T), cytosine (C), and guanine (G).

How are the two strands of DNA connected?

The two strands of DNA are connected through hydrogen bonds between the nitrogenous bases, with adenine (A) pairing with thymine (T) and guanine (G) pairing with cytosine (C).

What is the significance of the 5' and 3' notation in reference to DNA strands?

The 5' (5 prime) and 3' (3 prime) notation refers to the directionality of the DNA strand. It indicates the carbon atoms on the sugar molecule to which the phosphate group is attached, with the 5' carbon being at one end and the 3' carbon at the other.

Why is DNA replication essential for cells?

DNA replication is essential for cells because it allows for the duplication of genetic material, ensuring that each new cell formed during cell division receives a complete set of genetic information.

What is the role of the enzyme Helicase in DNA replication?

Helicase is an enzyme that unwinds the double helix of DNA by breaking the hydrogen bonds between the base pairs, creating a replication fork that allows the DNA strands to be used as templates for new DNA synthesis.

What is the difference between the leading and lagging strands during DNA replication?

The leading strand is synthesized continuously in the 5' to 3' direction as the DNA unwinds, while the lagging strand is synthesized in the opposite direction and requires the use of RNA primers and multiple short fragments called Okazaki fragments, which are later joined together.

Who discovered DNA and what was their contribution?

DNA was discovered by Swiss biologist Friedrich Miescher in 1869. He found a substance he called nuclein, which later became known as nucleic acid. However, the structure and significance of DNA were further elucidated by many scientists, including Rosalind Franklin, who confirmed the helical structure of DNA using x-ray diffraction.

Why is Rosalind Franklin's contribution to the understanding of DNA significant?

Rosalind Franklin's contribution is significant because she used x-ray diffraction to confirm the helical structure of DNA and to determine the arrangement of the sugar-phosphate backbone. Her work was crucial for understanding DNA's structure, even though she did not receive full recognition during her lifetime.

How does the DNA replication process handle errors?

DNA replication has a proofreading mechanism where DNA polymerase can remove and replace incorrect nucleotides that do not match the template strand, thus maintaining the accuracy of the genetic information being copied.

Outlines

00:00

🧬 The Wonders of DNA Structure and Function

This paragraph introduces DNA as a complex and vital molecule, highlighting its mesmerizing beauty and the fact that it wasn't until 60 years ago that its structure was fully understood. It explains that DNA is a 6-billion letter code within every living organism, stored in the cell's nucleus and composed of nucleotides, which include a sugar molecule (deoxyribose), a phosphate group, and one of four nitrogenous bases (adenine, thymine, cytosine, and guanine). The paragraph also describes the double helix structure of DNA, with its sugar-phosphate backbone forming the 'rungs' of the ladder and the nitrogenous bases forming the 'steps', adhering to specific pairing rules (A-T and G-C). It concludes with the vastness of DNA in the human body, emphasizing its importance in defining who we are.

05:01

🔬 DNA Replication and the Role of Scientists

This section delves into the process of DNA replication, a crucial aspect of cell division. It uses a quiz format to illustrate the concept of complementary base pairing in DNA. The paragraph then contrasts DNA with RNA, highlighting the differences in structure, sugar composition, and base components. It also provides a brief history of DNA discovery, acknowledging the contributions of various scientists, particularly Rosalind Franklin, whose work was instrumental in understanding DNA's helical structure but was overshadowed by the more famous duo, Watson and Crick. The paragraph emphasizes the complexity and elegance of DNA, its replication process, and the importance of scientific collaboration and recognition.

10:03

🧬🔧 The Mechanism of DNA Replication

This paragraph explains the intricate process of DNA replication, detailing the role of enzymes such as helicase and DNA polymerase. It describes the replication fork, the leading and lagging strands, and the challenges faced in replicating the latter due to its 3' to 5' directionality. The paragraph introduces the concept of RNA primers, necessary for initiating DNA synthesis, and the role of Okazaki fragments in the discontinuous replication of the lagging strand. It also touches on the proofreading ability of DNA polymerase, ensuring the accuracy of replication, and concludes by emphasizing the remarkable efficiency and accuracy of DNA replication within the human body.

Keywords

💡DNA

DNA, or deoxyribonucleic acid, is the molecule that stores the genetic instructions for all living organisms. It is the video's central theme, as it is described as the most complicated and important molecule. The script uses DNA to explain how genetic information is encoded and replicated, emphasizing its role in defining individual characteristics and the biological processes within cells.

💡Double Helix

The double helix is the iconic structure of DNA, likened to a twisted ladder in the script. It is composed of two polynucleotide chains coiled around each other. The concept is integral to the video's narrative, illustrating the physical form of DNA and how its structure contributes to its function in storing genetic information.

💡Nucleotides

Nucleotides are the building blocks of DNA, consisting of a sugar molecule (deoxyribose), a phosphate group, and a nitrogenous base. The script explains that linking these units forms a polynucleotide, which is the backbone of the DNA molecule. Nucleotides are essential for understanding the composition of DNA and its replication process.

💡Nitrogenous Bases

Nitrogenous bases are components of nucleotides that play a crucial role in the genetic code. The script identifies four bases in DNA: adenine (A), thymine (T), cytosine (C), and guanine (G). These bases form specific pairs (A-T and G-C) that are vital for the structure and replication of DNA, as well as for the transmission of genetic information.

💡Chromosomes

Chromosomes are structures within cells that contain a single DNA molecule, tightly packed with proteins. The script mentions that human somatic cells have 46 chromosomes each, emphasizing the organization of genetic material within cells and how chromosomes relate to the overall genetic makeup of an individual.

💡Replication

DNA replication is the process by which DNA makes a copy of itself, which is critical for cell division. The script describes replication as a rapid and accurate process, using the metaphor of a book being copied to explain how every cell in the body contains a complete set of DNA.

💡Helicase

Helicase is an enzyme that 'unzips' the DNA double helix by breaking the hydrogen bonds between base pairs. The script humorously compares helicase to a teenage boy wanting to 'unzip your genes,' highlighting its role in the replication process by unwinding the DNA helix.

💡RNA

Ribonucleic acid, or RNA, is a nucleic acid similar to DNA but with key differences, such as being single-stranded and containing the base uracil instead of thymine. The script introduces RNA as a related molecule that plays a crucial role in protein synthesis and DNA replication, contrasting it with DNA to emphasize their distinct functions.

💡Base Pairing

Base pairing refers to the specific bonding between nitrogenous bases in DNA, with adenine pairing with thymine and guanine with cytosine. The script explains base pairing as a fundamental aspect of DNA structure, essential for maintaining the integrity of genetic information during replication.

💡Okazaki Fragments

Okazaki fragments are short segments of RNA-primed DNA that are synthesized on the lagging strand during replication. The script uses the term to describe the discontinuous nature of lagging strand synthesis, illustrating the complexity of the DNA replication process.

💡DNA Polymerase

DNA polymerase is an enzyme that adds nucleotides to a DNA strand, following the template provided by the original strand. The script describes DNA polymerase as having a proofreading function, correcting errors during replication, and as being involved in both the leading and lagging strand synthesis, emphasizing its critical role in ensuring the accuracy of genetic information.

Highlights

DNA is described as the most complicated and potentially the most important molecule, with a mesmerizing double helix structure.

The true appearance of DNA was unknown until about 60 years ago, emphasizing its complexity and recent discovery in the grand scheme of scientific history.

Unraveling DNA from a single cell can result in a length taller than a human, highlighting the vastness of genetic material contained in the body.

The DNA in the human body, if stretched out, could reach the sun 600 times, showcasing the immense scale of genetic material.

DNA is a 6-billion letter code that provides the assembly instructions for every aspect of an individual.

Each human somatic cell contains 46 chromosomes, each with a large DNA molecule, packed with proteins in the cell nucleus.

DNA and RNA are both nucleic acids, the fourth major group of biological molecules, with DNA having a complex job in storing genetic information.

DNA is composed of nucleotides, which include a five-carbon sugar molecule, a phosphate group, and one of four nitrogen bases.

The genetic coding that defines an individual is found among the four nitrogenous bases: adenine, thymine, cytosine, and guanine.

DNA exists as a pair of molecules held together in a double helix structure, likened to a twisted ladder.

The sugar-phosphate backbone of DNA runs in opposite directions, creating a 5' to 3' pattern essential for replication.

DNA replication is a highly efficient process, capable of creating thousands of DNA copies in a few hours.

Helicase is the enzyme that unwinds the DNA helix, enabling replication by breaking hydrogen bonds between base pairs.

DNA replication involves the use of an RNA primer by the enzyme RNA primase to initiate the construction of the new DNA strand.

The lagging strand of DNA is copied in segments due to the directionality of DNA polymerase, requiring multiple RNA primers and subsequent ligation.

DNA polymerase has proofreading capabilities to correct errors during replication, maintaining the integrity of genetic information.

The discovery and understanding of DNA's structure involved numerous scientists over nearly a century, with Rosalind Franklin playing a pivotal yet underrecognized role.

James Watson and Francis Crick are often credited with discovering DNA's structure, but the journey was collaborative and spanned many contributors.

DNA's replication process and its proofreading ability underscore its complexity and the importance of maintaining genetic accuracy.

The episode concludes by emphasizing DNA's status as the most celebrated molecule of all time due to its fundamental role in life.

Transcripts

It's just beautiful, isn't it? It's just mesmerizing. It's double hel-exciting!

You really can tell, just by looking at it, how important and amazing it is.

It's pretty much the most complicated molecule that exists, and potentially the most important one.

It's so complex that we didn't even know for sure what it looked like

until about 60 years ago.

So multifariously awesome that if you took all of it from just one of our cells and untangled it,

it would be taller than me.

Now consider that there are probably 50 trillion cells in my body right now.

Laid end to end, the DNA in those cells would stretch to the sun.

Not once...

but 600 times!

Mind blown yet?

Hey, you wanna make one? (oh dear god)

Of course you know I'm talking about deoxyribonucleic acid, known to its friends as DNA.

DNA is what stores our genetic instructions -- the information that programs all of our

cell's activities.

It's a 6-billion letter code that provides the assembly instructions for everything that

you are.

And it does the same thing for pretty much every other living thing.

I'm going to go out on a limb and assume you're human.

In which case every body cell, or somatic cell, in you right now, has 46

chromosomes each containing one big DNA molecule.

These chromosomes are packed together tightly with proteins in the nucleus of the cell.

DNA is a nucleic acid.

And so is its cousin, which we'll also be talking about, ribonucleic acid, or RNA.

Now if you can make your mind do this, remember all the way back to episode 3, where we talked

about all the important biological molecules:

carbohydrates, lipids and proteins. That ring a bell?

Well nucleic acids are the fourth major group of biological molecules, and for my money

they have the most complicated job of all.

Structurally they're polymers, which means that each one is made up

of many small, repeating molecular units.

In DNA, these small units are called nucleotides. Link them together and you have yourself a

polynucleotide.

Now before we actually put these tiny parts together to build a

DNA molecule like some microscopic piece of Ikea furniture, let's

first take a look at what makes up each nucleotide.

We're gonna need three things:

1. A five-carbon sugar molecule

2. A phosphate group

3. One of four nitrogen bases

DNA gets the first part its name from our first ingredient, the sugar

molecule, which is called deoxyribose.

But all the really significant stuff, the genetic coding that makes you YOU,

is found among the four nitrogenous bases:

adenine (A), thymine (T), cytosine (C) and guanine (G).

It's important to note that in living organisms, DNA doesn't exist

as a single polynucleotide molecule, but rather a pair of molecules that

are held tightly together.

They're like an intertwined, microscopic, double spiral staircase.

Basically, just a ladder, but twisted. The famous Double Helix.

And like any good structure, we have to have a main support.

In DNA, the sugars and phosphates bond together to form twin backbones.

These sugar-phosphate bonds run down each side of the helix but, chemically, in opposite directions.

In other words, if you look at each of the sugar-phosphate backbones, you'll see that

one appears upside-down in relation to the other.

One strand begins at the top with the first phosphate connected to the sugar molecule's

5th carbon and then ending where the next phosphate would go, with a free end at the

sugar's 3rd carbon.

This creates a pattern called 5' (5 prime) and 3' (3 prime).

I've always thought of the deoxyribose with an arrow, with the oxygen as the point.

It always 'points' from from 3' to 5'.

Now on the other strand, it's exactly the opposite.

It begins up top with a free end at the sugar's 3rd carbon and the phosphates connect to the

sugars' fifth carbons all the way down.

And it ends at the bottom with a phosphate.

And you've probably figured this out already, but this is called the 3' to 5' direction.

Now it is time to make ourselves one of these famous double helices.

These two long chains are linked by the nitrogenous bases via relatively weak hydrogen bonds.

But they can't be just any pair of nitrogenous bases.

Thankfully, when it comes to figuring out what part goes where, all you have to do is

remember is that if one nucleotide has an adenine base (A),

only thymine (T) can be its counterpart (A-T).

Likewise, guanine (G) can only bond with cytosine [C] (G-C).

These bonded nitrogenous bases are called base pairs.

The G-C pairing has three hydrogen bonds, making it slightly stronger than the A-T base-pair,

which only has two bonds.

It's the order of these four nucleobases or the Base Sequence that allows your DNA

to create you.

So, AGGTCCATG means something completely different as a base sequence than, say, TTCAGTCG.

Human chromosome 1, the largest of all our chromosomes, contains a single molecule of

DNA with 247 million base pairs.

If you printed all of the letters of chromosome 1 into a book, it would be about 200,000 pages

And each of your somatic cells has 46 DNA molecules tightly packed into its nucleus

-- that's one for each of your chromosomes.

Put all 46 molecules together and we're talking about roughly 6 billion base pairs

.... In every cell!

This is the longest book I've ever read.

It's about 1,000 pages long.

If we were to fill it with our DNA sequence, we'd need about 10,000 of them to fit our

entire genome.

POP QUIZ!!!

Let's test your skills using a very short strand of DNA.

I'll give you one base sequence -- you give me the base sequence that appears on

the other strand.

Okay, here goes:

5' -- AGGTCCG -- 3'

And... time's up.

The answer is:

3' -- TCCAGGC -- 5'

See how that works? It's not super complicated.

Since each nitrogenous base only has one counterpart, you can use one base sequence to predict what

its matching sequence is going to look like.

So could I make the same base sequence with a strand of that "other" nucleic acid,

RNA?

No, you could not.

RNA is certainly similar to its cousin DNA -- it has a sugar-phosphate backbone with

nucleotide bases attached to it.

But there are THREE major differences:

1. RNA is a single-stranded molecule -- no double helix here.

2. The sugar in RNA is ribose, which has one more oxygen atom than deoxyribose, hence the

whole starting with an R instead of a D thing.

3. Also, RNA does not contain thymine. Its fourth nucleotide is the base uracil, so it

bonds with adenine instead.

RNA is super important in the production of our proteins, and you'll see later that

it has a crucial role in the replication of DNA.

But first...

Biolo-graphies!

Yes, plural this week!

Because when you start talking about something as multitudinously awesome and elegant as

DNA, you have to wonder:

WHO figured all of this out?

And how big was their brain?

Well unsurprisingly, it actually took a lot of different brains, in a lot of different

countries

and nearly a hundred years of thinking to do it.

The names you usually hear when someone asks who discovered DNA are James Watson and Francis

Crick.

But that's BUNK. They did not discover DNA.

Nor did they discover that DNA contained genetic information.

DNA itself was discovered in 1869 by a Swiss biologist named Friedrich Miescher.

His deal was studying white blood cells.

And he got those white blood cells in the most horrible way you could possibly imagine,

from collecting used bandages from a nearby hospital.

It's for science he did it!

He bathed the cells in warm alcohol to remove the lipids,

then he set enzymes loose on them to digest the proteins.

What was left, after all that, was snotty gray stuff that he knew must be some new kind

of biological substance.

He called it nuclein, but was later to become known as nucleic acid.

But Miescher didn't know what its role was or what it looked like.

One of those scientists who helped figure that out was Rosalind Franklin, a young biophysicist

in London nearly a hundred years later.

Using a technique called x-ray diffraction, Franklin may have been the first to confirm

the helical structure of DNA.

She also figured out that the sugar-phosphate backbone existed on the outside of its structure.

So why is Rosalind Franklin not exactly a household name? Two reasons:

1. Unlike Watson & Crick, Franklin was happy to share data with her rivals. It was Franklin

who informed Watson & Crick that an earlier theory

of a triple-helix structure was not possible, and in doing so she indicated that DNA may

indeed be a double helix.

Later, her images confirming the helical structure of DNA were shown to Watson without her knowledge.

Her work was eventually published in Nature, but not until after two papers by Watson and

Crick had already appeared in which the duo only hinted at her contribution.

2. Even worse than that, the Nobel Prize Committee couldn't even consider her for the prize

that they awarded in 1962 because of how dead she was.

The really tragic thing is that it's totally possible that her scientific work may have

led to her early death of ovarian cancer at the age of 37.

At the time, the X-Ray diffraction technology that she was using to photograph DNA required

dangerous amounts of radiation exposure, and Franklin rarely took precautions to protect herself.

Nobel Prizes cannot be awarded posthumously. Many believe she would have shared Watson

and Crick's medal if she had been alive to receive it.

Now that we know the basics of DNA's structure, we need to understand how it copies itself,

because cells are constantly dividing, and that requires a complete copy of all of that

DNA information.

It turns out that our cells are extremely good at this -- our cells can create the

equivalent 10,000 copies of this book in just a few hours.

That, my friends, is called replication.

Every cell in your body has a copy of the same DNA. It started from an original copy

and it will copy itself trillions of times over the course of a lifetime, each time using

half of the original DNA strand as a template to build a new molecule.

So, how is a teenage boy like the enzyme Helicase?

They both want to unzip your genes. (Hank why)

Helicase is marvelous, unwinding the double helix at breakneck speeds, slicing open those

loose hydrogen bonds between the base pairs.

The point where the splitting starts is known as the replication fork, has a top strand,

called the leading strand, or the good guy strand as I call it

and another bottom strand called the lagging strand, which I like to call the scumbag strand,

because it is a pain in the butt to deal with.

These unwound sections can now be used as templates to create two complementary DNA strands.

But remember the two strands go in opposite directions, in terms of their chemical structure,

which means making a new DNA strand for the leading strand is going to be much easier

for the lagging strand.

For the leading, good guy, strand an enzyme called DNA polymerase just adds matching nucleotides

onto the main stem all the way down the molecule.

But before it can do that it needs a section of nucleotides that fill in the section that's

just been unzipped.

Starting at the very beginning of the DNA molecule, DNA polymerase needs a bit of a

primer, just a little thing for it to hook on to so that it can start building the new

DNA chain.

And for that little primer, we can thank the enzyme RNA primase.

The leading strand only needs this RNA primer once at the very beginning.

Then DNA polymerase is all, "I got this"

and just follows the unzipping, adding new nucleotides to the new chain continuously,

all the way down the molecule.

Copying the lagging, or scumbag strand, is,

well, he's a freaking scumbag.

This is because DNA polymerase can only copy strands in the 5' -- 3' direction,

and the lagging strand is 3' -- 5',

so DNA polymerase can only add new nucleotides to the free, 3' end of a primer.

So maybe the real scumbag here is the DNA polymerase.

Since the lagging strand runs in the opposite direction, it has to be copied as a series

of segments.

Here that awesome little enzyme RNA Primase does its thing again, laying down an occasional

short little RNA primer that gives the DNA Polymerase a starting point to then work backwards

along the strand.

This is done in a ton of individual segments, each 1,000 to 2,000 base pairs long and each

starting with an RNA primer, called Okazaki fragments after the couple of married scientists

who discovered this step of the process in the 1960s.

And thank goodness they were married so we can just call them Okazaki fragments instead

of Okazaki-someone's-someone fragments.

These allow the strands to be synthesized in short bursts.

Then another kind of DNA Polymerase has to go back over and replace all those RNA Primers

and THEN all of the little fragments get joined up by a final enzyme called DNA Ligase. And

that is why I say the lagging strand is such a scumbag!

DNA replication gets it wrong about one in every 10 billion nucleotides.

But don't think your body doesn't have an app for that!

It turns out DNA polymerases can also proofread, in a sense,

removing nucleotides from the end of a strand when they discover a mismatched base.

Because the last thing we want is an A when it would have been a G!

Considering how tightly packed DNA is into each one of our cells, it's honestly amazing

that more mistakes don't happen.

Remember, we're talking about millions of miles worth of this stuff inside us.

And this, my friends, is why scientists are not exaggerating when they call DNA the most

celebrated molecule of all time.

So, you might as well look this episode over a couple of times and appreciate it for yourself.

And in the mean time, gear up for next week, when we're going to talk about how those

six feet of kick-ass actually makes you, you.

Thank you to all the people here at Crash Course who helped make this episode awesome.

You can click on any of these things to go back to that section of the video.

If you have any questions, please, of course, ask them in the comments or on Facebook or Twitter.