The Cell Cycle (and cancer) [Updated]

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Have you ever been sitting in class and thought to yourself, “I wonder what my skin cells are doing right now at this very moment? " This kind of pondering may be unique to me…maybe…but wouldn’t we at some point wonder what are cells are doing right now? Because if you remember, as part of the cell theory, you are made of cells.

All living things are made of 1 or more cells! Many multicellular organisms, like you, have cells that work together. Working together as part of body tissue.

Body tissues working together as part of an organ. Organs working together as part of an organ system. Your cells are specialized to work in these different levels of organization---you have skin cells, stomach cells, muscle cells just to name a few---and their functions need to be regulated.

These cells actually are regulated as part of something called the cell cycle and that is going to relate to my question of, “I wonder what my cells are doing right now. ” Cells themselves can grow in size. But let’s put it in perspective now: a multicellular organism isn’t growing because each individual cell is getting bigger.

A multicellular organism itself grows by making more cells---by the cells making more cells by dividing. That’s cell reproduction. One reason that you’re bigger than you were when you were 5---unless you are 5---is because your cells have divided to make more cells.

Mitosis, and the cytokinesis that follows that splits the cytoplasm, allows you to make new body cells but you don’t want that cell division happening all the time. Why? It is likely that the term ‘cancer’ may have relevance to you.

We have had family members that have battled cancer before- it is definitely a relevant topic for all of us. Cancer is in part due to cells that divide too frequently. The cells are not regulated; they are uncontrolled.

Cancer cells can have other problems too---they might not be able to communicate with other healthy cells, they may not be able to carry out normal cell functions, they may not securely anchor themselves like other cells do which can make them more likely to travel somewhere else. Some cancer cells have the ability to secrete their own growth hormone. that makes blood vessels divert over to those cancer cells and supply the cancer cells with nutrients, which can take nutrients away from healthy cells.

Why do cancer cells become this way? Well, there is a lot of research in this area. With some cancers, there may be genetic links making some cells more susceptible to having problems—these genetic factors might run in families.

Exposure to toxins, radiation, or excessive exposure to UV light can be risk factors for some cells to become cancerous. The uncontrolled growth that cancer cells have gives rise to more cells like them, which can develop into a tumor. Some tumors stay put but some do not.

Now the good news is that scientists continue to develop better treatments which include destroying the cancer cells with radiation or medication---such as chemotherapy--- which will target cells that divide frequently. Maybe someday you will be part of helping to meet the challenge of trying to eliminate cancer, because the fact remains that these cells are not participating in the cell cycle like they should. So what is the cell cycle?

The cell cycle is often represented as a pie chart like this. Cells are either in one of two different phases: a phase called interphase where the cells themselves are growing, replicating their DNA, doing their cell functions---- or they are in M phase which includes mitosis and the actual splitting of the cytoplasm - cytokinesis. So this M phase is where cells actually divide to make more cells.

But cells spend most of their time in interphase. So most of the time, they’re not dividing. Now, depending on what kind of cell, it might do mitosis more or less often; for example, your hair follicle cells do mitosis frequently which is why your hair can grow at the rate that it does.

It’s also why many cancer drugs may also target hair follicle cells, because many cancer drugs go after cells that do cell division frequently. It’s a big deal for cells to hit this M phase. If a cell has an error---a harmful mutation for example---you do not want it to divide because then it will create another cell that has this same issue (harmful mutation).

That’s where check points come in handy. Along the cell cycle there are check points to check that the cell is growing well and replicating its dna correctly and doing everything it’s supposed to correctly before it divides. To better understand those checkpoints, let’s further divide this cell cycle pie chart.

We have G1 (Gap1), S (synthesis), G2 (Gap 2)---all three of those are part of interphase. Then we have M phase where mitosis will happen. During G1, the cell individually itself grows.

Then it replicates its DNA in S phase…you can remember that because the "s" is for “synthesis” which means to make something, and it’s making DNA. Then G2, the cell grows some more in preparation for mitosis. So let’s take a look at checkpoints.

We got one here in G1---this checkpoint checks, “Is the cell growing well enough? ”—“Is its DNA damaged? ” Because if it is, you definitely don’t want it to move on to S phase where you would replicate DNA.

Does the cell have the resources it needs if it were to keep moving on? This checkpoint in G2 checks if the DNA was replicated correctly back in S phase. Is it growing well enough---does it have the resources it needs to continue?

Okay then, moving on, this next checkpoint in M phase is my favorite checkpoint. It checks in the stage metaphase to make sure that chromosomes, which are made up of DNA, are lined up in the middle correctly---that they’re all attached to the spindle correctly. Because if they’re not, the chromosomes will not be separated correctly.

So now you may have two big questions. First, what happens if the cell doesn’t meet the requirements of the checkpoint and second, what is doing the regulating of this cycle anyway? To address the first question- if the reason the cell can’t go past the checkpoint is a reason that can be fixed, the cell may kind of pause here until it can fix the issue.

But if it can’t be fixed? Then the cell does something called apoptosis which basically means the cell self destructs. This ensures that a cell that is damaged beyond repair will not go on to divide.

So what is doing the regulating anyway? We’ve mentioned before that proteins are a big deal. Genes in your body can code for proteins that do an assortment of functions, and there are many proteins involved with regulating the cell cycle.

Some of them are positive regulators because they allow moving forward in the cycle and some are negative regulators that may make things stop. The proteins themselves can be sensitive to cues inside and outside of the cell. So, for example, two proteins that are involved in positive regulation are cyclin and Cdk.

Cdk is specifically an enzyme protein---a fancy kind called a kinase which is worth a google. Cdk can have different forms of cyclin protein bound to it. Different types of cyclin rise and fall throughout the cell cycle, and the rising and falling is based on a variety of signals to determine when the cell should move on to the next cell cycle phase.

Typically each cell cycle phase---G1, S, G2, M---- will tend to have a different cyclin binding with the Cdk. The rise and fall of cyclin types and the role CdK has when it’s active is a fascinating subject to explore. Remember that vocabulary word we said, “Apoptosis?

” Proteins that are negative regulators -for example, a protein called p53- can be involved in initiating apoptosis. Again, we encourage you to explore beyond this video. One last thing to mention.

There are some cells that don’t go through the phases we mentioned, because they’re actually in G0. That’s a zero by the way and not an o…because if it was an o then it’d say go and G0 is kind of the opposite of that. G0 is a resting phase.

Now cells here are still performing cell functions, but they’re not preparing to divide. Some cells go here temporarily, maybe if there’s not enough resources around for example. But some---like many types of neurons in your brain and spinal cord may stay here permanently.

If they stay here permanently, they’ll never get to M phase so they will not divide. This can be one reason why a major injury to the brain or spinal cord can have challenges with healing as many of those cells may not be able to replicate. A topic that definitely continues to be researched.

Well, that’s it for the amoeba sisters, and we remind you to stay curious.