DNA Structure and Replication (P Herrera)

[#(text-style:"bold")+(text-style:"buoy")[Welcome!]] --- You are a scientist in the far future, and have been assigned the task of observing DNA molecules way up close. After exploring the nucleus, you come across a DNA molecule. [[Observe it]] (set: $name to (prompt: "What is your name?", ""))

As you observe the DNA Molecule, you see it is double stranded and made of nucleotides. [[Look closer at strands]] [[Look closer at nucleotides]] [[Continue with observation|DNA Replication Begins]]

The strands each have a 5' end and a 3' end. The 5' end has a phosphate group attached to the deoxyribose of the nucleotide, while the 3' end has a hydroxyl group attached. The strands also run anti-parallel, with one strand running from 5' to 3' and another running from 3' to 5'. (if: (history:) contains "Look closer at nucleotides")[ [[Continue Further Observation|DNA Replication Begins]]]\ (else:)[ [[Look closer at nucleotides]]]

The nucleotides are constructed of deoxyribose, a phosphate group, and a nitrogenous base (either adenine, thymine, cytosine, or guanine). They are held together by hydrogen bonds. (if: (history:) contains "Look closer at strands")[ [[Continue Further Observation|DNA Replication Begins]]]\ (else:)[ [[Look closer at strands]]]

[(text-style:"buoy")+(b4r:"solid")+(b4r-size:2)+(b4r-colour:white)[You must correctly guide the DNA molecule through replication in order to fulfill your task.]] [[Continue|First Step]]

As you observe the DNA molecule, you notice something strange happening. You realize that the DNA is beginning to replicate itself! This process will take us from one starting molecule to two daughter molecules, with newly formed double helix containing one new strand and one old strand. [[Continue to observe]]

Since the DNA molecule is just beginning to replicate, what must it first do in order to get the process started? [[Tear the DNA strands apart]] [[Unzip the double helix structure]] [[Dissolve the hydrogen bonds and nucleotides]]

Nope! You cannot tear the strands apart- there is another way to do continue this replication! [[Go back|First Step]]

Good choice! Unzipping the double helix is completed by an enzyme called helicase, which breaks the hyrdogen bonds of the complementary DNA bases. Now, the starting DNA is in two seperate strands. What kind of shape must these strands result in so that the unzipping can continue? [[Y-Shape]] [[Semi-circle]] [[X-shape]]

Nope, this wouldn't work! While you do need to break the hydrogen bonds, you cannot completely dissolve the nucleotides. [[Go back|First Step]]

Good! The seperated strands formed a Y-shape, which is also called the replication forks. The forks are moved forward by helicase, which is working to unwind the DNA. However, there is a chance the DNA could rewind back together and form the double helix again. What should be done to fix this potential issue? [[Use positive and negative charges to keep strands apart]] [[Move each strand far away from each other]] [[Coat the replication forks with single strand binding proteins]]

Not quite! A different shape is made! [[Go back|Unzip the double helix structure]]

This wouldn't work, something else is in play that keeps the DNA from rewinding! [[Go Back|Y-Shape]]

Good call! The starting DNA can keep going with its replication without the risk of rewinding. Now, a molecule called DNA polymerase (which is responsible for synthesizing DNA) will come into play. Polymerase attaches nucleotides to the //3' end//. However, it is not as simple as that, since the polymerase cannot make DNA from scratch. They need something more to actually add nucleotides to! What does the DNA polymerase need? [[A primer]] [[A 5' end]]

Correct! The polymerase needs a primer to attach the nucleotides to. An enzyme called primase makes the RNA primer, which is a 5-10 nucleotides long stretch of nucleic acid complementary to the template that provides a 3' end for DNA polymerase to work on. Once this primer is binded to the end of a strand, DNA polymerase extends it with more nucleotides and creates a new DNA strand. However, the process of making new strands is different for each strand. [[Continue with leading strand]] [[Continue with lagging strand]]

Nope, something different is needed! [[Go back|Coat the replication forks with single strand binding proteins]]

The 5' to 3' strand is synthesized in the ''same direction'' as the replication fork, and it is called the //leading strand//. Once the primer binds to the end of the leading strand, DNA polymerase binds to the strand and adds new complementary nucleotide bases in the 5' to 3' direction. This replication is continuous. (if: (history:) contains "Continue with lagging strand")[ [[Move on]]]\ (else:)[ [[Continue with lagging strand]]]

The other 5' to 3' strand, synthesized in the ''opposite direction'' from the movement of replication fork, is called the //lagging strand//. This strand is made in fragments because the DNA polymerase (which is moving away from the replication fork) has to come off and reattach itself to the exposed DNA. This means that the strand is made in fragments called //Okazaki fragments//, and requires a new primer for each fragment. (if: (history:) contains "Continue with leading strand")[ [[Move on]]]\ (else:)[ [[Continue with leading strand]]]

Nice, the new strands are synthesized! But, there are a few more proteins and enzymes needed in order for everything to go smoothly. What should be used to make sure the DNA polymerase of a lagging strand doesn't float away when a fragment is re-started? [[Sliding clamp protein]] [[RNA strands]] [[Spindle fibers]]

Good job, the sliding clamp protein will work perfectly to hold the DNA polymerase from floating off! Now that we have the sliding clamp working, we can shift our focus to making sure that the DNA double helix ahead of the replication fork does not get too tightly wound up. What should be used to do this? [[New DNA strands]] [[Leftover fragments]] [[Topoisomerase]]

Not exactly, something else is needed. You can wave goodbye to the polymerase, though. [[Go back|Move on]]

No, these aren't used, something different is used! [[Go back|Sliding clamp protein]]

Yep! Topoisomerase is an enzyme which prevents the double helix from supercoiling by making temporary nicks in the helix to relieve tension, and sealing the nicks to avoid any permanent damage. Once this is complete, only clean-up is left over! [[Clean up]]

The only clean up required is removing the RNA primers and replacing them with DNA (using DNA polymerase I) and sealing the gaps between DNA fragments with DNA ligase! [[Next]]

[(text-style:"buoy")[#''Congratulations, $name!!'']] --- (text-style:"smear")[You have perfectly guided the DNA molecule through replication!!]