Control of the Cell Cycle - Online Tutor, Practice Problems & Exam Prep

The cell cycle consists of distinct phases regulated by proteins called cyclins and cyclin-dependent kinases (CDKs). Cyclins activate CDKs, which phosphorylate target proteins to control cell division. Key checkpoints—G1, S, G2, and M—ensure proper progression and DNA integrity. Regulation of CDKs occurs through inhibitors, phosphorylation, and cyclin levels, with the anaphase-promoting complex degrading cyclins when no longer needed. This intricate control prevents uncontrolled cell division, which can lead to cancer.

Overview

Hello everyone. In this lesson, we are going to be talking about the cell cycle and the mechanisms that are utilized to control the processes in the cell cycle. Okay. So, the cell cycle is going to be these different major stages that the cell goes through when it is deciding and preparing for cellular division. And of course, cellular division needs to be controlled, right? Because what is uncontrollable cellular division? It's going to be cancer. So obviously, we don't want that. So our cells are going to have many regulators and many control mechanisms to ensure that the division of cells doesn't get out of control.

So cell cycle controls rely on a core group of switches. You can think of them as switches, but they're going to be proteins that turn things on and off like a switch does. And they're going to turn certain proteins on, certain proteins off, and this is going to determine the steps in the cell cycle. So the most important determinant and control of the cell cycle that you are going to need to know are going to be the cyclins. And these are going to be these little proteins that turn protein kinases on and off. And they are going to vary in their concentration, but they're not going to vary in their activity. So, they're going to vary in concentration in the cell, but they're not really going to vary in activity. So I'm going to tell you why this is important in just a second.

So there are many different types of cyclins. I'm going to teach you about 4 types of cyclins and the different types of cyclins are going to become incredibly prominent and then they're going to die down in different stages of the cell cycle and this is going to control those stages of the cell cycle. So that's why I said they vary in concentration. But the job of each cyclin is dependent on the type of cyclin that it is and it doesn't change.

So what does a cyclin do? A cyclin is this little protein that is going to affect the cyclin-dependent kinases or CDKs. Cyclin-dependent kinases do exactly what their name says. Remember kinases, phosphorylate, or dephosphorylate proteins. And this is going to turn proteins on or turn proteins off. And these kinases are switched on or off by cyclin. That's why they are cyclin-dependent kinases. A cyclin will bind to the CDK, and it will allow the CDK to activate itself and begin doing its job.

So the cell cycle controls the protein kinases based on the types of cyclins that are activating that cyclin-dependent kinase. So you may be wondering what that would look like. What that would look like would be something like this. We have our CDK. So, CDK. And then, we're going to have the little cyclin cyclin, and the cyclin-dependent kinase is going to turn on. So this is cyclin. And it is turned on and now this is activated. And this means that the cyclin-dependent kinase can then phosphorylate or dephosphorylate certain proteins which will have different jobs in the process of the cell cycle.

So the important thing to know about the CDKs is they do not vary in concentration. So, do not vary in concentration. They are always in the cell and their levels within the cell remain the same, but the cycling concentrations do not. The cycling concentrations constantly change, but the CDKs are always there. They're always waiting to be activated.

Cyclins. Can see all of this graph. These are 4 different cyclins and we have a, b, d, and e cyclin. And you can see that during the different phases g1, s, g2, and mitosis of the cell cycle, these are different phases. You can see that these cyclins greatly vary in their concentration.

Now if I were to show you the concentration of CDKs, it would be something like this. These would be CD, CDK concentrations. And the CDK concentrations don't change. They're always there in the same amount, but the cycling concentrations do change and it depends on which stage in the cell cycle the cell is in.

So that is some basis on the CDKs and the cyclins. So now, let's scroll down and let's look at those different stages of the cell cycle. And let's talk about something interesting and very important for those stages of the cell cycle.

We are going to talk about checkpoints. So checkpoints are stages within the cell cycle that the CDKs actually do their job. So there are many different checkpoints. There are 4 here, but, I'm going to go over 5. I didn't list the M checkpoint because it's pretty self-explanatory. I'll tell you guys about it in just a second. So there's the G1 checkpoint, the Start checkpoint, the S checkpoint, and the G2 checkpoint.

So remember, in g1, which we can see down here. In g1, let me show you this cell cycle diagram. So this is g one. Right. Here. G one phase and then here is the g one checkpoint. Remember in g1 phase the cell is deciding whether it wants to divide or not. And the way it determines this is it looks at its cell size, its nutrients level, and its growth factors, and if it has any DNA damage. If it sees that any of these characteristics are not good enough for cellular division it will not go into cellular division. So that's what the g one checkpoint is looking for. It's checking all of these things. It's activating CDKs to check all of these different characteristics And once it has passed through the checkpoint and seeing that everything is fine, then it will proceed on to S phase.

So S phase is going to be here in green and the S checkpoint is right at the end of S phase. Now once the cell has decided it wants to go and divide itself, it can't go back. There's no going back at this point. It's all or nothing. Once it enters S phase, it's done. It's going to start dividing. So s phase, remember that this is DNA replication phase or synthesis replicate or synthesis of DNA phase and, basically, you're replicating the DNA inside of the cell, so there's enough DNA in there for the 2 new daughter cells. And the s checkpoint is going to ensure that the DNA replication went through properly, and nothing really detrimental happened, and that replication has ended. That's the S checkpoint.

Once the S checkpoint has been completed, then the cell will move on to the G2 phase. Which is right here, and we have our G2 checkpoint. Now, G2 is going to be whenever the cell is getting ready for the physical division process of mitosis. So this is going to ensure that the DNA has completely been replicated. Any DNA damage that was created during s phase is going to be fixed. Any mutations are going to be fixed, and it's going to repair anything that needs to be repaired before the cell enters into mitosis.

So then, we have M Phase, which is relatively short. Oh, you can't really see the M whenever I use that color. So this is M phase. I'll write it in here. M phase. M phase is mitosis and we're going to have our spindle checkpoint or our M checkpoint. Basically, the spindle checkpoint is between metaphase and anaphase, and it's just ensuring that the chromosomes are correctly attached to the spindles before they are separated and pulled to the poles of the cell. So the spindle checkpoint doesn't have as much to do with CDKs and cyclins as the other checkpoints, so that's why we didn't really list it above, but it is an important checkpoint to know.

But, this is going to be the overview of the cell cycle. And, this is going to be the cycle that a cell will take whenever it wants to ensure that the DNA to ensure that the DNA is repaired and ready to go before s phase, and it makes sure that the cell actually wants to divide and has all the nutrients that it needs. Then we have the starting point at the end of g1. Remember I talked about this? If the cell decides to go into s phase, it's going to continue on through mitosis. There is no stopping after this point. Then we have the s checkpoint, and this is a pause in the s cycle to ensure that the DNA replication is happening correctly, and that it is coming to completion. And then g 2 checkpoint is a pause right before mitosis, just to make sure that everything is ready to go before the cell physically divides itself during the process of mitosis.

Now, there are going to be cyclin proteins that are associated with these transitions and stages in the cell cycle. And I listed those for you here. We have the G1S Cyclins, we have the G1 Cyclins, the S Cyclins, and the M Cyclins, and they're going to be very important for these different stages. So, whenever we have the G1 Cyclins, these are going to control the G1 and S Cyclins, and they're really just these cyclins are very important for ensuring the G1 phase goes correctly, and it actually ensures that all of the phases of the cell cycle actually proceed correctly. And I'll show you an image of that in just a second.

And then, we are going to have the G 1 s cyclins, and these are going to activate CDKs in late g 1, and this is going to trigger the beginning of the s phase. This is going to trigger that transition into cellular division. This is the starting point where we can't turn back. And these g one S Cyclins are going to bind to CDKs and trigger that start point.

Then we're going to have the S Cyclins, which are going to activate CDKs after the start to stimulate the replication of DNA. So these S cyclins are going to bind to the CDKs and then the CDKs are then going to phosphorylate and turn on all of the proteins that are needed for s phase or the replication of DNA.

And then we're going to have our M Cyclins, and these are going to trigger mitosis. So these M Cyclins are going to bind to the CDKs, and this is going to activate all of the proteins that are needed for mitosis. So see here that the type of cyclin that is utilized is going to activate the CDK, which will then activate proteins associated with that cyclin. M cyclins activate M proteins or mitosis proteins. S cyclins activate proteins for cellular DNA replication. G 1 cyclins are going to control that transition from g 1 into s, and then g 1 s cyclins are going to do the same thing. And they're going to activate proteins that are needed to begin the process of cellular division. I hope that makes sense.

So we have these different cyclins. What is their concentration going to look like? Well, remember this picture we saw up here. These are actually referring to these different cyclins. So, the G1 cyclins are actually here in red. G1 cyclins are kind of unique because they're pretty much needed for the whole process and the different stages of the cell cycle, but they're incredibly and integrally important for the G1 phase. But they're unique because they're needed for all of the phases.

And then, you can see in green. These are going to be the G1s Cyclins which are needed for that transition from G1 to S phase. And then you're going to have the S cyclins here in blue. Which are needed for the replication of DNA and the repair of gna DNA that is happening in G2 phase before mitosis. So that's why there's high concentrations of S Cyclins in S Phase and G2 Phase because the DNA is being replicated in S Phase, and it's being repaired in G2 Phase. Now, the final set of cyclins here in orange are going to be the M cyclins, and they are going to come to a peak in concentration right at the start of mitosis. So, all of those mitosis proteins have been phosphorylated and turned on, and that whole process can begin. So this is how the cyclins that are different and unique to each stage are going to change in concentration throughout the cell cycle.

Now, I know that I went over a lot in this video. I hope it was helpful. Just remember that cyclins are utilized for the control of the cell cycle. There are different types of cyclins that control the different stages of the cell cycle, and cyclins activate CDKs. And the type of cyclin determines which proteins will be activated by the CDK proteins. And this is going to ensure that the cell cycle goes correctly, that none of the phases are messed up and that the process of cellular division is controlled and doesn't get out of hand. Okay, everyone. Let's go on to our next topic.

Regulation

Okay. So now we're going to talk about regulation, but specifically regulation of the cyclin-dependent kinases themselves. So this is kind of a double level of regulation. Right? We're talking about cell division and mitosis and how the CDKs regulate that. So how do we regulate the CDKs? There are three main ways. And the first is a little weird, but also probably the most important. And so, this is through the CDK inhibitor phosphate. Now, this might sound a bit weird. Right? Because when we think about adding phosphates to proteins, what do we think of? We think of activating them. Kinases add phosphates; they activate. But this is a special type of phosphate, and it acts as an inhibitor. So instead of activating, it does the exact opposite. Instead, that phosphate has to be removed; it has to be dephosphorylated in order to become active. That means that CDKs actually need to be phosphorylated at one site and dephosphorylated at another site to become active. The protein responsible for dephosphorylating or removing these phosphates is called CDC25, and that removes the inhibitory phosphate. This is a little different than anything else we've mentioned in this course, or really probably anything you've seen before, but is a really important mechanism of CDK regulation.

Now, the second one is kind of, it just feels like it makes sense. There are CDK inhibitors. These are proteins. They bind to CDKs usually when they're in complex with cyclins, and they block their function. This acts like every other inhibitor we've talked about, right. It just it's an inhibitor, it binds to it, it blocks its function, but it has a second way of CDK regulation.

And then finally, the third way is going to be through cyclin levels. So if cyclin levels are high, then you're going to have active CDKs, but if they are low, cyclin levels are low, then you're going to have inactive CDKs. This is because cyclins activate CDKs. So if you have high cyclin levels, you're going to have high activity, but if you have low cyclin levels, you're going to have low activity. So then the question is, well, how do you regulate cyclin levels? Well, typically, they just get degraded. So, there's this complex called the anaphase-promoting complex, and this actually degrades M and S cyclins by labeling them with ubiquitin, targeting them for destruction. Anaphase here. It's degrading these M, it's degrading these S cyclins that have stimulated the cell cycle, but are no longer needed. So then slowing down the cell cycle and getting ready to stop it, essentially.

So here is that unique mechanism that I've talked about, you probably never seen before. So here we have a CDK, CDK1, and it has an activating phosphate, but it also has this inhibiting phosphate. So if we were just to take this complex, what's in my arrows? Not anything to do with this one down here. Just what's in my bracket. Is this CDK1 in my bracket, is this active or inactive? Right. So this is an inactive complex because it has the inhibiting phosphate. Now, once the protein, remember what protein this is, CDC25. Once it comes in and removes this phosphate, thatleadstoactivation. So as soon as this phosphate is gone, it's no longer inhibiting, and so you get activation of CDK1. And this happens for a lot of different CDKs. So those are the three ways that CDKs are regulated so that then they can go on and regulate the serious cell cycle. So now let's turn the page.

Often, Cdks have to be dephosphorylated to become activated.

• A. True
• B. False

Which of the following cell cycle checkpoints occurs immediately before the start of S phase?

• A. G₁
• B. S
• C. M

Which of the following proteins is responsible for removing the inhibitory phosphate on Cdks?

• A. S cyclins
• B. APC
• C. M cyclins
• D. Cdc25

Here’s what students ask on this topic:

What are the main stages of the cell cycle and their functions?

The cell cycle consists of four main stages: G1, S, G2, and M. In the G1 phase, the cell grows and decides whether to divide based on size, nutrients, and DNA integrity. The S phase is where DNA replication occurs, ensuring each daughter cell receives a complete set of chromosomes. The G2 phase involves further growth and preparation for mitosis, including DNA repair. Finally, the M phase (mitosis) is where the cell physically divides into two daughter cells. Each stage is regulated by specific cyclins and cyclin-dependent kinases (CDKs) to ensure proper progression and prevent errors.

How do cyclins and CDKs regulate the cell cycle?

Cyclins and cyclin-dependent kinases (CDKs) are crucial for cell cycle regulation. Cyclins are proteins whose concentrations vary throughout the cell cycle, while CDKs are enzymes that remain constant. Cyclins bind to CDKs, activating them. Once activated, CDKs phosphorylate target proteins, driving the cell through different stages of the cycle. For example, G1 cyclins help the cell prepare for DNA replication, S cyclins promote DNA synthesis, and M cyclins trigger mitosis. This precise regulation ensures orderly cell division and prevents uncontrolled growth, which can lead to cancer.

What are the key checkpoints in the cell cycle, and what do they monitor?

The cell cycle has several key checkpoints: G1, S, G2, and M. The G1 checkpoint assesses cell size, nutrient availability, growth factors, and DNA damage to decide if the cell should proceed to DNA replication. The S checkpoint ensures that DNA replication is complete and accurate. The G2 checkpoint verifies that DNA replication is finished and repairs any damage before mitosis. The M checkpoint, or spindle checkpoint, ensures that chromosomes are correctly attached to the spindle apparatus before being separated. These checkpoints prevent errors and ensure proper cell division.

How are CDKs regulated in the cell cycle?

CDKs are regulated through three main mechanisms: phosphorylation, CDK inhibitors, and cyclin levels. CDKs require phosphorylation at one site and dephosphorylation at another to become active. The protein cdc25 removes inhibitory phosphates, activating CDKs. CDK inhibitors are proteins that bind to CDK-cyclin complexes, blocking their function. Cyclin levels also regulate CDK activity; high cyclin levels activate CDKs, while low levels inactivate them. Cyclins are degraded by the anaphase-promoting complex, which tags them with ubiquitin for destruction, ensuring timely cell cycle progression.

What role do cyclins play in the cell cycle?

Cyclins are proteins that regulate the cell cycle by activating cyclin-dependent kinases (CDKs). Different cyclins are present at various stages of the cell cycle, ensuring specific processes occur at the right time. For example, G1 cyclins help the cell prepare for DNA replication, S cyclins promote DNA synthesis, and M cyclins trigger mitosis. Cyclin levels fluctuate throughout the cycle, rising and falling to activate or deactivate CDKs as needed. This regulation ensures orderly cell division and prevents errors that could lead to uncontrolled growth or cancer.