CELL CYCLE

"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 our cells are doing right now? If
you remember, as part of the cell theory, we are all made of cells. All living things are made
of one 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, and muscle
cells just to name a few, and their functions need to be regulated. These cells 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. However, a multicellular organism isn't growing because
each individual cell is getting bigger. A multicellular organism itself grows by making more
cells, and the cells make more cells by dividing. That's cell reproduction.

One reason that you're bigger than you were when you were five years old is because your
cells have divided to make more cells. Mitosis, and the cytokinesis that follows to split the
cytoplasm, allows you to make new body cells.

Still, you don't want that cell division happening all the time. Why? It is likely that you have
heard the term 'cancer' before. We have had family members that have battled cancer,
and it is definitely a relevant topic for all of us. Cancer is in part due to cells that divide too
frequently. Cancer 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, and
they may not be able to carry out normal cell functions.

Cancer cells also 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, which makes blood vessels divert over to those cancer cells and
supply the cancer cells with nutrients. This 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 can give rise to more cells like them, which can
develop into a tumor. Some tumors stay put, but some do not.

Fortunately, 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. Cells are either
in one of two different phases. They are either in a phase called interphase where the cells
themselves are growing, replicating their DNA, and doing their cell functions; or, they are
in M phase, which includes mitosis (division of the nucleus) and cytokinesis (actual splitting
of the cytoplasm).

It is M phase where cells actually divide to make more cells. Still, cells spend most of their
time in interphase. So, most of the time, cells are not dividing.

Now, depending on what kind of cell, it may do mitosis more or less often. Your hair follicle
cells do mitosis frequently which is why your hair can grow at the rate that it does. This is
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, it can divide to create another cell that would also have this harmful mutation.
That's where check points come in handy. There are check points along the cell cycle to
check that the cell is growing well, replicating its DNA correctly, and doing everything it's
supposed to do correctly before it divides.

To better understand those checkpoints, let's consider the phases in the cell cycle. We
have G1 (Gap1), S (synthesis), and G2 (Gap 2). Those phases are all part of interphase. Then
we have M phase where mitosis and cytokinesis will happen.

During G₁, the cell individually itself grows.

Then the cell replicates its DNA in S phase. You can remember that because the "s" is for
"synthesis," which means to make something. The cell is making more DNA!

Then in G2, the cell grows some more in preparation for mitosis.

So let's consider the checkpoints. We have a checkpoint in G 1. This checkpoint checks

several factors. Is the cell growing well enough? Is its DNA damaged? If the DNA is
damaged, you definitely don't want it to move on to S phase where it 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. It checks that the chromosomes are all attached to the
spindle correctly. 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? 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. What 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. Some are negative regulators
that can make things stop.

The proteins themselves can be sensitive to cues inside and outside of the cell. 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 researching! 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 the vocabulary word apoptosis? Proteins that are negative regulators, such as a
protein called p53 for example, 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 Go- That's a zero by the way and not an "o,"
because if it was an o, then it'd say go and Gois kind of the opposite of that. Go is a resting
phase. Cells in Go are still performing cell functions, but they're not preparing to divide.
Some cells go here temporarily. They may do this if there are not enough resources around
for example. However, some cells, 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. This is
a topic that continues to be researched.