Paper 3- DNA Replication Factory

A Tour of the DNA Replication Factory
A Children’s Story

Watson was pretty much your average kid. He went to school and played with his friends just like you and me. But unlike you and me, Watson did not live in a city or town, he lived in a cell. That’s right, a cell. In fact, the cell was sort of like a city of its own. His family lived in a small house in East Cytoplasm, which was near the Golgi factory where his father worked. Every day, his father would go off to work packaging vesicles at the Golgi factory, and Watson would go to school. Watson enjoyed school because he thought learning was fun and he could hang out with his best friend, Crick.
One day, Watson woke up unusually excited. He had remembered that that day at school was no ordinary day. This day was his class field trip to the DNA replication factory. He had been looking forward to this field trip for many weeks and was very excited that the day had finally come. He had been learning about DNA replication in school and was eager to see all the cool machines it up close.
He hurriedly finished his breakfast and headed off to school. As he walked down the microtubule to school, he kept thinking about how cool the replication machines had seemed as he was learning about them in class. When he got to school, he immediately found Crick. “I can’t wait to go the factory today,” he said, “how about you, Crick.” “Me neither,” replied Crick, “I really want to see the polymerase machine; that’s my favorite.”
Finally the teacher came into the room and said, “Alright class, the day you’ve been waiting for is finally here. When we go to the factory, I expect you all to be on your best behavior. DNA replication is a complicated process and it’s very important that it is done right.” So the whole class got onto the bus and headed off to the factory.
When they got to the factory, they were greeted by the factory’s tour guide. “Ok boys and girls, I hear you’ve been learning about DNA replication in class. Before we go inside, can anyone tell me the four main machines used here at the factory?” Watson raised his hand and answered, “helicase, primase, polymerase, and ligase.” “That’s right,” said the tour guide, “and now let’s see how they all work.” She opened the large door to the factory and led the class inside.
“Wow, there it is!” exclaimed Watson. The machine was huge. Long chains of nucleotides were being twisted and split, and machines were doing many different things all at the same time. It was almost too much to take in at once. Some machines were breaking DNA, some machines were putting it together, and other machines were preparing the DNA to be copied.
“We’ll start by looking at the helicase machine,” said the tour guide. She walks over to a giant strand of DNA wound tightly into a double helix. “It looks kind of like a spiral staircase,” said Crick. “Yes, it does,” replied the tour guide. She pointed to a large machine spinning DNA like a jet engine, splitting the double helix in two pieces. “This is the helicase machine; it splits the DNA into two complementary strands.”
“What do you mean by complementary?” asked Watson. “Well,” answered the tour guide, “DNA is made of four different pieces, called bases: A, T, G, and C. A always pairs with T, and G always pairs with C. So, in a strand of DNA such as AGT, the complementary strand would be TCA.” “Oh, I see,” said Watson, “That’s clever.”
The tour guide continued, “The helicase machine begins splitting the DNA strand at certain places called origins of replication. The split in the strand is called the replication fork. Helicase attaches to the strand and continually feeds the DNA through the machine, breaking apart the bases so they can be copied.
“”But what keeps the split strands apart?” asked Crick. “Ah,” replied the tour guide, “we use single-stranded binding proteins to hold the strands apart while we work of them. It actually works very well.”
The tour guide then moved on to the next part of the factory. “This is the polymerase machine,” she said, “this is where the new bases are actually added to the split strands to form two new strands.” Watson looked at the awesome machine with amazement. It was taking bases from a huge pool and attaching them to the DNA strands as they were fed through the machine.






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“What’s that other machine in front of the polymerase machine doing?” asked Watson. “Oh, that’s the primase machine,” said the tour guide. “You see the polymerase machine can’t start creating a new strand all on its own, so primase adds a primer made of RNA to get the polymerase machine started. You can think of it like when you use primer to coat something to get it ready to be painted.”
Then Watson noticed something quite strange. After the replication fork, the complementary DNA strands were being fed into the polymerase machine in opposite directions. One strand was going straight through, but the other strand was fed through backwards and looped around the machine.
“Why are the two strands being copied in opposite directions,” asked Watson. “That’s a very good question,” replied the tour guide. “The two DNA strands actually have two different ends; one is the 5’end, and the other is the 3’end. The strands are connected anti-parallel to each other, which means they run in opposite directions. As it turns out, the polymerase machine can only add to the strand on the 3’end. This causes the strands to elongate in an overall 5’to 3’direction, and the two strands are copied in different directions. You see, for the strand being copied in the direction toward the replication fork, the polymerase machine can copy it continuously, since there is nothing in its way. But for the strand being copied in the direction away from the replication fork, the polymerase machine can only copy a short segment of DNA each time, then it must wait for the helicase machine to unwind some more of the strand. The polymerase machine then starts again and forms another small segment. We call these segments Okazaki fragments.”
“That sounds very complicated,” said Watson. “It’s sort of like Lego blocks,” replied the tour guide. Each Lego has two different sides. Let’s say you build two long stacks of Lego blocks and lay them side by side in opposite directions, and you can only add to the top side of each stack. In order for the stacks to get bigger, they have to grow in opposite directions.” “Oh,” said Watson, “that makes sense.”
The tour guide then led the group to the next part of the factory, but Watson was still infatuated with the polymerase machine. He quietly stayed behind to get a better look at this base-pairing wonder. The machine was very complicated but also very interesting. There was a huge, shiny control panel with many buttons and switches on it. Being the curious type, Watson decided to experiment with the controls. He pressed one of the buttons to see what it would do.
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“Oh no!” cried Watson. He had accidentally directed the polymerase machine to pair a section of nucleotides incorrectly. Not knowing what to do, Watson ran back to the tour group. He knew he had made a huge mistake, but he didn’t want to get into trouble. He decided it would be better if he just didn’t say anything about his mistake. After all, no one could know for sure that it was him that did it.
The tour guide was now speaking about the ligase machine. “After the Okazaki fragments are formed,” she explained, “the ligase machine glues them together to form a single strand exactly like the other one. After that, the DNA replication process is complete. There are now two identical strands of DNA ready to be shipped out. Does anyone have any final questions?”
While some of the other students were asking questions, Watson couldn’t stop feeling guilty about his mishap with the polymerase machine. “Crick,” he said, “I think I’ve made a big mistake.” “What’s wrong,” asked Crick. “I think I may have caused a problem with the polymerase machine, but I don’t want to get into trouble.” “Look man,” said Crick, “If you think the DNA could be messed up, you have to tell someone. That’s pretty serious.” “I guess you’re right, replied Watson.”
Watson finally confessed his mistake to the tour guide. To his surprise, the guide was not very angry. She thanked him for his honesty and told him that the problem could be fixed. “We can use our nuclease machine to do what we call a nucleotide excision repair,” she said. “That’s where we cut out the damaged DNA with nuclease, replace the bases with polymerase, and reconnect the strand with ligase.”
The class watched as the repair was performed, then thanked the tour guide and headed back onto the bus to return to school. “What a day,” said Crick. “What a day, indeed,” replied Watson. He couldn’t wait to get home and tell his parents all about the day’s adventure and find out when his next field trip would be.