[Caitlin:] Felicia, we're rolling here. [Felicia:] Sorry, but my zipper is misbehaving. Yeah, I know. But I don't know, tell a joke or something. [Caitlin:] Tell a joke? Felicia, I'm a scientist, not a comedian. I can't just pull a rubber chicken out of my back pocket. [Felicia:] Hilarious. [Caitlin:] Glad you conquered that zipper. Now, you can join us. [Felicia:] Is it hot in here or is it just me? [Caitlin:] All that work for nothing. [Felicia:] Relax, it's no problem. I can always zip it right back up again. Luckily for us, DNA works in exactly the same way. [Caitlin:] Well, how else would it copy itself? [Felicia:] Well, how else would it copy itself? [Caitlin:] Cute. [Felicia:] Let's find out. Join us this week on... [Both:] DNA Decoded. [Music] [Felicia:] We've already seen how DNA is tightly packed into chromosomes that fit inside the nucleus of the cell. Today, we're going to take a look at how DNA replicates itself to create new cells. [Caitlin:] The genetic code inside DNA would stay locked inside itself, like a code book hidden in a vault, if it didn't have the ability to make exact copies of itself. [Felicia:] Scientists study DNA replication to learn more about how we transmit genetic information from one cell to another, and what happens when things go wrong. [Caitlin:] Another reason why scientists want to understand this process better is so that we can mimic it, or reconstruct it in a test tube. Imagine the possibilities if we could replicate DNA in the absence of a cell. [Felicia:] That would be pretty amazing. [Caitlin:] Okay, let's look at that process of replication, starting at the very beginning. Remember we untwisted the double helix of the DNA molecule into a ladder? Well, DNA unwinds just like that. The first step in replication is unzipping the double helix. [Felicia:] What do you mean by unzipping? [Caitlin:] Well, do you remember when we said that the bonds on the sides of the DNA ladder were super strong and the base pairs on the rungs of the ladder were held together by weaker bonds? Well, the weak bonds between the base pairs allow them to unzip, just like a zipper can. [Felicia:] Like my jacket. [Caitlin:] Yes, just like the zipper on your jacket. In fact, you know the slider on your zipper? Some very specific proteins called DNA helicases act like the slider on your zipper. Your DNA wouldn't be able to unzip without them. [Felicia:] Time to unzip some DNA. [Caitlin:] Okay. So, here's the DNA double helix. DNA helicase is an enzyme that breaks down the weak bonds between the nucleobases, and separates the DNA into two strands. The DNA strands are unzipped at both ends to create a replication bubble. But for now we're just going to focus on one strand, to make things clear. The separation of the helix creates what is known as a replication fork. The nucleobases are like the teeth of the zipper. [Felicia:] Do you remember when we said that DNA strands run in opposite directions? They are anti-parallel because at the end of one strand is a sugar, while the end of the other strand is a phosphate. [Caitlin:] Right. Well, in scientific speak, we say that one strand runs five prime to three prime, while the other strand runs three prime to five prime. [Felicia:] Got it. [Caitlin:] So, after helicase does its job, we now have two DNA strands running in opposite directions. The one at the top is running five prime to three prime, and the one at the bottom is running three prime to five prime. [Felicia:] Okay, I think I got it. What comes next? [Caitlin:] Okay. Next, a protein called primase marks the spot where replications should start with an RNA primer, which is just a small piece of RNA. We'll talk more about that in a bit. The DNA polymerase uses that RNA primer as a kicking-off point for the replication process. [Felicia:] DNA polymerase uses Watson-Crick rules to attach complimentary nucleobases to an unzipped strand of DNA. DNA polymerase adds base pairs moving from five prime to three prime, and so on, and so on, and so on. [Caitlin:] However, DNA polymerase can only work in one direction, from five prime to three prime. When DNA gets copied, the five prime to three prime strand, or what we call the leading strand, gets copied continuously. While the other strand has to be copied backwards, a few base pairs at a time, which is a slower process. The other strand is called the lagging strand. [Felicia:] Which is completely unfair in my humble opinion. [Caitlin:] Well, why is that? [Felicia:] Do you know Fred Astaire and Ginger Rogers? [Caitlin:] The dancers from the movies? Sure. [Felicia:] Okay. Someone once said, sure, Fred Astaire was great, but don't forget that Ginger Rogers did everything he did only she did it backwards and in high heels. [Caitlin:] That's a great point. [Felicia:] So, I like to think of the leading strand as a Fred Astaire strand and the lagging strand as Ginger Rogers. It's a little more complicated -- but just as elegant. If you're interested in what it's like to duplicate DNA backwards and in heels, check out the video in our supplementary materials. [Caitlin:] So, there you have it. In very simple terms, that's how one piece of DNA turns into two strands. It's a bit more complicated than that. There are a few more proteins and steps involved in the process, but they all work together to replicate DNA. [Felicia:] Do you know why they call this process of DNA replication semi-conservative? [Caitlin:] I don't but I'll bite. [Felicia:] You know how DNA is made up of two strands of DNA joined together in a double helix? [Caitlin:] Yep. [Felicia:] Now, we call these strands the parent DNA. After the parents cell divides, two daughters cells each contain a strand of the original pairing DNA and a new strand. This combination of something old and something new helps minimize mistakes. [Caitlin:] Well, for the most part.
