I have had a teaching challenge simmering in my head for a while now. How do I help students really understand the 5’/3′ aspect of DNA Replication? Yes, you can teach DNA replication and not really mention 5’/3′, but I think that helping students visualize how it actually happens (and why there are lagging and leading strands) is important. I wanted to design a simulation or some way to model DNA Replication. The idea that a nucleotide has a direction, a top and a bottom, is hard to visualize. And then it hit me. Lego® bricks have a top and a bottom. And they can stick together. And they come in a variety of colors so they would work great for showing 4 (5 including uracil) different nucleotides! So that’s it. I decided to write this fun blog post showing DNA Replication using my son’s Duplo bricks. My hope is that students and teachers will stumble upon this post and look at DNA replication is a new way.
First let’s start with the nucleotides:
The top (the part with the bumps) is the 5′ end. The bottom (no bumps) is the 3′ end. The DNA nucleotides are square and RNA nucleotides have a curve on one end, to distinguish them from each other. I used Blue (A), Yellow (T), Red (C), and Green (G) plus Orange (U).
Just like each nucleotide has 5′ end and a 3′ end, a strand or stack of nucleotides has a 5′ end and a 3′ end. The key is that nucleotides can ONLY be added to the 3′ end of the existing strand (or in the LEGO® brick world, the non bumpy side).
DNA is anti-parallel, meaning that when you look at both strands of a DNA helix, one strand has its 5′ end in one direction and the other strand has its 3′ end in that same direction.
Helicase starts to unwind or open-up the DNA helix! A replication fork opens up. (In LEGO® brick world, replication enzymes are just like Pokemon… they can only say their names. Apparently.)
As helicase continues to open up the DNA helix and separate the strands, primase jumps in and starts building short RNA sequences called primers. Notice as primase starts to build the new strands, the new strands form by adding nucleotides to the 3′ end of the existing strand. (A lot of students get confused here because the new strand being built has to be anti-parallel to the old strand it is being built next to.)
What keeps the old strands of DNA from sticking together after the helicase opens it up? There are other proteins called single strand binding proteins that stick to the single strands and keep them apart. (Note: some teachers don’t mention these in high school, but I thought it would be nice to put them here to show one additional detail and let students know that the process isn’t as simple as it looks in the typical high school textbook.)
After there are RNA primers in place, DNA Polymerase can start adding DNA nucleotides to the 3′ end of the primers. This means that one DNA Polymerase enzyme will be going in the same direction as the helices. As the helicase moves along, the DNA polymerase enzyme can follow right behind it and the strand that it builds is called the leading strand. On the other side (the top strand in the diagram) the 3′ end of the primer is facing away from the moving helicase, which means the polymerase that starts adding DNA nucleotides to that side must move away from the helicase. The strand formed by polymerases moving away from the helices is called the lagging strand.
As helicase continues to open up the DNA, primase starts to build another primer, closer to the helicase, further along the strand of DNA. DNA Polymerase builds onto this new primer and creates a new DNA fragment until it reaches the primer that was built earlier. These primer-DNA fragments are called Okazaki fragments and they form the lagging strand. The leading strand, the one created by the polymerase following the helicase, is created continuously.
This process continues until the helicase is finished opening up the helix. Primase adds primers on the lagging strand side and polymerase continues to add DNA nucleotides onto the primers. The leading strand polymerase continuously adds onto the leading strand. At the end, we have two new strands (still with RNA primers and gaps between fragments).
To complete the replication process, DNA polymerase does some editing and removes the RNA primers and replaces them with the right DNA nucleotides.To connect the fragments and remove the gaps, Ligase comes in and connects the fragments.
And at the end, there are two identical strands of DNA! Please note we didn’t really talk about telomerase and a few other aspects of DNA replication but I hope you enjoyed this blog post and learned a little about DNA Replication in the process.
Disclaimer: LEGO®is a trademark of the LEGO Group of companies which does not sponsor, authorize or endorse this site. I love LEGO Bricks and my son does too. Some of the bricks can be found in your local toy store. Some of the bricks used are from the 1980’s and are the original bricks I played with as a child.