 DNA replication is not for the weak at heart, but hopefully at this point, you're like, we kind of think it might be important to be able to make copies of DNA. And I would go back, except I probably would make you seasick to our first diagram of the human life cycle. And remember, we went from zygote to 100 trillion cells. I'm gonna write that down. We went from one cell, and that was the zygote, to 100 trillion cells, and that was the grown-up. And each cell has 46 chromosomes of DNA. Each cell has 46 pieces, molecules, of this double-stranded DNA. Each, okay, this is what's in one cell. That, the amount of DNA in there is six billion base pairs. Oh my Lord, are you kidding me? Six billion base pairs divided up in those various chromosomes. For perspective, not everybody's genome is the same size. We have six billion base pairs. The marble lungfish has the biggest genome that we've discovered, and it has 133 billion base pairs in every single cell. This is just mind-blowing. Six billion base pairs, every time a cell divides, six billion base pairs have to be copied. And that process is DNA replication. And in humans, for us, this whole process, one cell, it takes eight to 10 hours to copy all the DNA, I mean, yes, it should take a long time to make a copy of all of the DNA, and that copy of the DNA has to happen before the cell can divide, so that we make sure that each daughter cell, each cell that results has the complete set. Boy, if you're gonna make a copy, like if you had to copy a book that had six billion words in it, oh my Lord, and you had to, would you make any mistakes? Well, maybe I should ask you, do you think I would make any mistakes? I can't even say the words right when I'm giving these lectures to you. So yes, I would make mistakes. Your cells, the process of DNA replication makes about one, oh man, one mistake. I knew I had this fact somewhere per billion base pairs. So that means every time we copy our DNA, we're gonna have six base pairs that are different from what we had in the beginning. We will learn as we start talking about DNA function, we will learn what the significance of that, that's actually, those mistakes, those are mutations. And gloriously, mutations often don't even matter, and we will see why that is the case. How many molecules, how complicated do you think this process is to produce an entire copy of all of these chromosomes? It's a complicated process, and it happens in a method, I don't know what this is, but that process is called semi-conservative replication. And man, there are so many cool studies that they did to figure this stuff out. So it would be an awesome application task for you to check out the study. I think it was Stahl, someone in Stahl did this, Messelsen and Stahl figured out that DNA replication is semi-conservative, and you probably are going, dude, what does that even mean? Well, if you imagine, here's a double strand of DNA, right? Semiconservative replication means that the strand separates so that new nucleotides new nucleotides are added, like half of each new strand is new nucleotides, and the other half is the old original nucleotides. The alternative would be like conservative DNA would look like this, where somehow we went from that to oh my gracious, this. Okay, sorry for my DNA drawings, but you get the idea that this would be conservative. And then there is a proposal of dispersive replication, where you basically took one strand of DNA and your two resulting strands were like a mishmash of new DNA and old DNA, not the case. What they figured out is that it actually is a semi-conservative replication, and you end up, it makes sense, right? Because if you split the DNA apart and you now have an adenine exposed on one side and a thymine exposed on the other, when you add a thymine to this side and an adenine to this side, the two molecules that you create are identical. It's a, it's, how often am I, is my mind like blown? It happens all the time. Okay, so let's talk about the enzymes that are involved in this process. And I'm gonna make a list of them on this page that this, on this diagram that shows you, it's just nicer than my diagrams. Notice that this is my original DNA double strand. It separates out and we end up with two new strands being formed, and you can actually see, like, oh my God, that totally makes sense, that we have these nucleotides that are just getting added. There are a bunch of enzymes that are involved in this process, and I'm gonna list them out and tell you what their jobs are. The first enzyme to get involved is an enzyme called helicase. And basically helicase goes in and unzips the DNA. And that means, like, you can imagine, breaking, if you're unzipping the DNA, you're breaking the hydrogen bonds that connect the nitrogen bases. So helicase goes in and does that work. There's another guy, now helicase is there. Helicase is being shown by this, like, triangle in our diagram, unzipping the DNA. At the same time, we have a buddy named Topo isomerase. Well, I guess I'm not gonna write Topo isomerase for you. Can you see that well enough? Topo isomerase is a molecule that, like, imagine this. If you, I know you've done this, because I totally have done this. When you try to unravel a piece of rope, why have I done this? I don't know, but I definitely have. When you try to, like, separate out the strands of rope or yarn, if you just separate it, you get, like, it overwines. It's called supercoiling that happens above. Like, somehow you have to release the pressure, and you can either let the whole thing spin and that can let you continue unwinding your rope. Or you end up with a supercoiled mess up high and unraveled yarn down low. Does that, did I just confuse the crap out of you? Topo isomerase prevents supercoiling. So that, we don't have to worry about that happening. We do end up with these little binding proteins, and these guys keep the two strands from popping back together because they want to. It's cozier for DNA molecules to exist in a double helix. And so you can imagine all of this, all these enzymes doing this work, they're gonna need energy to make it happen, which means we need cellular respiration to be taking place. Okay, the majority of the work is done by an enzyme called DNA polymerase. And I probably, I'm gonna, this is it right here, and you'll notice that there's one on each strand. And the molecules totally like these enzymes divide and conquer. When they get the message that it's time to replicate the DNA, they start like replicating anywhere that they can find. They have many DNA polymerases that are getting after it and doing the job. They're all working together, and it still takes eight to 10 hours to do the whole thing. DNA polymerase is the main dog who does the building, adding in the nucleotides. And it builds a new strand in the five prime to three prime direction. So the new strand is, the new piece of DNA is being built in the five prime to three prime direction. Which means you have one of your strands, when you open it up, one of them is just gonna zip along. DNA polymerase is just gonna go brrr and be moving in the five prime to three prime direction and building new molecules. So behind them is growing five prime to three prime strand. The other side is gonna have to work backwards. Can you visualize this? Because the way, and you can see this here, we have the lagging strand is the one that goes slower. The leading strand, we can just zip along and make it happen. The lagging strand means that we end up building fragmentally. We produce these fragments on the lagging strand and they're called Okazaki fragments. Do you see that? I'll blow it up so you can see it really clearly and I'll erase my little line so that you know that's an O. That's Okazaki. Okazaki was named after a scientist and his wife who figured this out, those fragments. And so this brings in another enzyme that we're gonna need. Those fragments need to be put back together again and the enzyme ligase, what seals, connects. Connects Okazaki fragments. There's somebody else. There's somebody else folks. Primase. This is super interesting. DNA polymerase can't go unless there is an RNA. Primer laid down first. So the whole thing isn't gonna happen unless we lay down an RNA primer and primase does that. I think what you'll find is that the names of the enzymes match their functions. So it isn't DNA primase is gonna lay down primers that will allow the whole thing to get started because here's the fact that DNA polymerase can't function unless it has an RNA primer to start with. Next step, if you're looking at this going like that, then don't worry because what we're gonna do next is we're gonna walk through another rig style animation of this whole process where we'll see the molecule of DNA, we'll separate it out, we'll watch. DNA polymerase, we'll watch helicase do that work. We'll watch the DNA polymerase bring in the nucleotides and add new nucleotides. We'll watch the lagging strand get the pieces put together. We'll watch the primase lay down the RNA primers and we'll see it all in order. Someone removes the primers, the RNA primers and I can't remember who does that. Okay, are you ready to go do some animation? I am.