AP Biology The Cell Cycle

Welcome to Educator.com. I am Dr. Carleen Eaton, and today is the first of three lessons on cell reproduction.0000

We are going to start out by talking about the cell cycle.0008

Functions of cell division or cell reproduction include the reproduction of an organism, the growth of an organism and repair.0012

Certain cells of the body, such as those in skin or liver, can actually divide.0022

If you get a cut or an injury, nearby skin cells could divide and help you to heal the same with the liver, so one function of cell division is repair.0028

As we are going to discuss later on, certain very specialized cells, such as neurons, lose their ability to divide, so they can no longer divide and repair in that way.0040

Another function of cell division is reproduction. For example, bacterial cells divide via binary fission.0052

Binary fission is a means of a sexual reproduction, and prokaryotes reproduce via binary fission.0062

Organisms that reproduce sexually create gametes via a particular type of cell division called miosis.0073

Miosis creates gametes such as sperm and egg.0084

Fertilization unites the sperm and egg to create a zygote, which will undergo mitosis, another type of cell division0096

and, thereby, grow into an embryo, a fetus and continue to grow until adulthood.0108

Here, we see reproduction. Cells are reproduced via cell division and growth, so an organism starting out smaller, dividing via mitosis, cell division and specialization of cell types.0115

This is just a general overview, and we are going to go into each type of cell division, miosis, mitosis.0134

And then, later on in the course, when we talk about prokaryotes, I will discuss binary fission.0141

It is important to know some terminology as we go along.0146

When we discuss the cells produced via mitosis and miosis, these are called daughter cells, and mitosis produces a different number of daughter cells than miosis.0149

And again, we will go into all of these details, so remember the term daughter cells, I will use that throughout the course.0162

Another thing to be aware of is that in order for cells to divide, all of the cell's genetic material must be duplicated.0171

In addition, the cytoplasm, organelles, proteins and other components of the cell must be replicated.0181

Duplication of DNA has to occur and does occur in one phase of the cell cycle.0187

And additional organelles, cytoplasm, cell membrane are all made to provide enough material for the daughter cells.0192

Right now, we are going to be focusing on eukaryotic cell division.0203

And since eukaryotes have genetic material that is organized into chromosomes, you need to understand chromosomes and chromosome structure in order to understand cell reproduction.0207

Let's take a look at the structure of chromosomes.0218

The genetic material or DNA in eukaryotic cells is organized into chromosomes, and this actually shows a chromosome that has already had its DNA replicated.0221

And I can tell that because this chromosome consists of two sister chromatids.0234

This is one sister. This whole section is a sister chromatid, and this is the other chromatid, so sister chromatids.0241

The sister chromatids are connected by, what is called a centromere, and the centromere is located here in the middle, so the centromere.0255

And the chromosome, overall, is composed of chromatin, so if you are just looking at...no, what is a chromosome made out of? Chromatin.0271

This is DNA plus protein, so the DNA is actually wound around a special type of protein called histones, so histone proteins plus DNA are known as chromatin.0283

At certain points in the cell cycle, the chromatin becomes very highly condensed.0299

And when it is highly condensed, it is visible via light microscopy in the form that you may have seen photos of, which this shows a sketch of- what a typical chromosome looks like.0305

At other points in the cell cycle, it is just chromatin that is less tightly coiled.0317

Again, here we have a chromosome with two sister chromatids, but I want to point out that if you saw something like this, this is still a complete chromosome.0322

This is one chromosome, and it has only one chromatid on it. This is also considered only one chromosome.0335

It has two chromatids, so it is one chromosome with two chromatids, but these are completely attached; and they are identical.0352

These two chromatids are identical. They contain the same genetic information.0365

So, even though, this has more chromatids, it is still a single chromosome, and this becomes very important when we discuss the differences between miosis and mitosis,0369

understanding that what a chromatid is, what constitutes a chromosome and how many of these that you have, differentiates miosis and mitosis.0380

Again, you start out with a single chromatid on the chromosome. The DNA is replicated at a particular step in the cell cycle, and you will end up with still one chromosome but duplicate information.0392

Each section of the chromosome is called an arm, so this is the short arm.0409

You will hear referred to the short arm of, say, chromosome 20, so the chromosomes are numbered.0414

In humans, in our somatic or most of the cells on our body, other than reproductive cells, are somatic cells, contain 46 chromosomes, and you can hear them called by their number.0419

There is actually 2 sets of 23 chromosome- 2 sets of 23.0431

And this the long arm and the short arm, so the long arm of a particular chromosome, the short arm. This is the long arm and the short arm of its sister chromatid.0440

With that understanding, let's go on and just talk generally about the outcomes of mitosis and miosis, and then, there will be a lecture covering each of these in great detail.0450

Mitosis results in two identical daughter cells, and it conserves the chromosome number.0462

Two types of cell division: one is mitosis, and with mitosis, you will start out with a cell that, let's say, has, for this cell, four chromosomes.0472

Mitosis will occur, and you will end up with daughter cells that have the same number of chromosomes, so conservation of chromosome numbers.0489

In addition, these daughter cells are identical to the parent cells. They are identical in chromosome number.0505

They are also identical in the information that the chromosomes contain. They are identical to each other.0513

They are identical to the parent cell. This is much different than miosis.0518

Miosis occurs to produce gametes, so mitosis produces somatic cells. Somatic cells are all the cells in the body that are not reproductive cells.0525

Liver cells are somatic cells. The cells in your eye, your skin, your kidney, those are all somatic cells.0540

They are just the regular cells of the body.0546

Miosis results in the production of gametes, so gametes are produced via miosis; so miosis produces gametes, in other words, sperm and egg.0550

These are sometimes also called germ cells.0566

In miosis, cells that are going to produce sperm or egg will undergo miosis, and let's say that a particular cell starts out with four chromosomes.0571

With miosis, there is actually two rounds of cell division, and the result will be 1, 2, 3, 4 daughter cells.0588

And each of these, will only have half the number of chromosomes.0602

Here, we started out with 1, 2, 3, 4. Here, I am just going to end up with 1, 2, 1, 2 chromosomes in each, and these are non-identical.0608

Starting out with four chromosomes, ending up with only two, so the daughter cells are non-identical.0623

They are different from each other, and they are different from the parent cells.0634

Let's look at the cell cycle overall because mitosis only takes up a small portion of the cell cycle.0645

There are two major phases in the cell cycle, and the cell actually spends 90% of its time in a phase called interphase, so 90% of its the time in interphase and only 10% in the M phase.0652

Mitosis is part of the M phase, and we talk about mitosis a lot because that is where a lot of the interesting stuff happens.0669

That is when the chromosomes are divided into the daughter cells. However, the cells actually spend most of its time in interphase.0679

Let's first look at the different parts of interphase. There are three parts to interphase: G1, S and G2.0689

G1 stands for Gap 1. S phase is synthesis, and G2 is Gap 2.0696

During interphase, growth occurs, so interphase is growth of the cell, and if the cell is going to divide into daughter cells, as I mentioned before, not only does it need to duplicate its DNA.0711

It needs to make more cytoplasm, proteins, cell membrane components, mitochondria, Golgi apparatus, and that is what is occurring during these phases.0726

During G1, there is growth. There is duplication of organelles, increase in cytoplasm, increase in the size and volume of the cell.0737

The cell moves on to S phase, and I want to be clear that the growth continues.0748

The duplication of the organelles and everything continues, but something else that is very important happens as well.0756

Synthesis S phase, DNA replication occurs.0760

DNA replication occurs, so that there will be enough DNA for each of the daughter cells.0766

After S phase, the cell goes into another gap phase. This one is called G2/Gap 2, and during this time, there is continued growth.0773

The cell will, again, duplicate organelles, continue to increase in size, and then, by the end of Gap 2, the cell has everything it needs to produce daughter cells.0784

This is all interphase, and now, we are in the M phase. There are two portions of M phase: mitosis and cytokinesis.0795

Mitosis is the section of the cell cycle during which the chromosomes are divided up into two separate sets, one for each nuclei of the daughter cell.0804

Here, we have separation of chromosomes. The chromosomes are divided up into two pairs, or not two pairs, two complete sets, one for each nuclei of the daughter cells.0819

Now, cytokinesis is the actual separation of what was one cell into two cells.0840

So now, we have two sets of chromosomes. Everything we need for two cells, but it is still just one cell.0846

The cell pinches off in the middle. The cytoplasm divides, and you end up with two daughter cells.0853

Cytokinesis is the actual physical separation into two cells.0859

Cytokinesis actually starts during late mitosis. It is, sometimes, considered a part of mitosis or telophase.0863

Sometimes, it is written as an extra step afterwards. Either way, it is part of M phase.0871

And you have to remember, these divisions into phases, mitosis or these cytokinesises are arbitray. It is something scientists use to help them discuss and categorize and study the cell cycle.0877

But, in nature, things are more continuous, and there is not these absolute separations.0889

Mitosis and cytokinesis, there is some overlap in these processes.0895

I mentioned before that certain cells such as neurons do not divide.0900

Very highly specialized cell do not divide, so what do they do? Where are they in the cell cycle?0905

Well, they are rested in quiescent phase known as G0. G0 is just a resting state, in which cells do not proceed through the cell cycle.0911

The cells that are in this state or sometimes called post-mitotic cells because G0, that phase is after mitosis.0924

Sometimes, G0 is considered just an extension of the G1. Other times, you will just see it written here as just immediately post mitosis.0933

Either way, G0 is a quiescent resting phase that non-dividing cells stay in.0943

Let's focus a little bit more on cytokinesis. Again, after the cell has duplicated its organelles, duplicated its DNA and then, gone through mitosis, what will happen is,0952

you will have this one cell that is, now, larger than it started out with and two sets of chromosomes, one for what is going to be the nuclei of each daughter cell.0963

But now, these cells need to separate. This cell needs to separate into two daughter cells, and it does that in animals through what is called a cleavage furrow.0976

A cleavage furrow forms down the middle of the cell, and that is this indentation that you see here. This groove is the cleavage furrow.0988

Actin and myosin pinched off the cell in the middle. Remember that actin and myosin are proteins that are also important for the contraction of muscle and for different kinds of movements.1005

One of their functions is to interact in such a way that this cleavage furrow deepens and pinches off, and then, you end up with two physically separate daughter cells- 1, 2, 3, 4, 1, 2 ,3 ,4.1016

And as you will see here, there are four chromosomes, but each only has one chromatid on them; and we will see why in the mitosis lecture.1039

Now, plant cells function a little bit differently as far as cell division, and that is because they have cell walls.1049

Instead of forming a cleavage furrow, what happens with plants is that they form what is called a cell plate.1055

In telophase, vesicles that are formed by the Golgi apparatus start to coil less near the middle of this cell.1064

These vesicle will coil less, and what they contain are components to build a cell wall.1074

This cell plate, then, forms, and a cell wall can be built between what are going to be the two daughter cells; and then, those will divide into two daughter cells.1082

But they stay closely associated with each other, and plants the two daughter cells; and they are actually stuck together.1092

Plant cells, the division is a little bit different. Again, it involves a cell plate versus a cleavage furrow.1101

One very important topic is that of control of the cell cycle because different cells divide at different rates. Certain cells like skin are rapidly dividing.1110

They will go into the cell cycle a couple times in one day even. They have a rapid turnover.1122

Other cells like neurons are rested in one phase of the cell cycle, and if the cell cycle is not tightly controlled, the result will be out of control growth and sometimes cancer.1126

Let's talk about how the cell cycle is regulated.1140

There are cytoplasmic signalling molecules that regulate the cell cycle, and there are also other internal and external factors that regulate the cell cycle,1144

first, focusing on just these cytoplasmic signalling molecules and what is called checkpoints.1152

These molecules constitute what you will hear called a cell cycle control system. Its name tells you what it does - controls or regulates the cell cycle.1158

There are checkpoints in the cell cycle, and these occur at G1, G2 and M phase.1168

Checkpoints are points where the cell stops and waits for a "go ahead" signal.1173

When you look at the cell cycle, that schematic of it, you see that there is G1, S, G2, and you might think that "OK, the cell just moves through".1181

It does G1. It finishes.1191

It goes on to S phase, then, it goes straight to G2; but that is not actually the way it happens.1193

The cell does not automatically move from one phase to the next phase. In fact, it stops after a certain phase.1200

It waits. If it gets a "go ahead" signal, it goes to the next phase.1208

If it does not, it stays there.1214

You can think of this as like a stop light. At these different checkpoints, the cell gets to the checkpoint, the light is red.1217

It waits for a specific signal that is analogous to a green light. When it gets that signal, it goes to the next phase.1225

The most important checkpoint in mammalian cells is the G1 checkpoint. This is often called the restriction point.1233

If a cell receives the "go ahead" signal in the form of these cytoplasmic signalling molecules,1241

the cell will generally advance on through G1, S phase, G2, M phase and end up dividing into two daughter cells.1249

It is very likely if the cell used to go ahead at this point, that it will complete the cycle.1259

If no "go ahead” is given at this restriction point, the cell will stay in G0 quiescent phase and remain there.1265

Alright, what are these cytoplasmic signalling molecules?1274

We know that at least some of them are cyclins and cyclin-dependent kinases.1281

Recall in a previous lecture, I mentioned that kinases are proteins that phosphorylate other proteins, so kinases phosphorylate other proteins.1286

In doing so, these kinases can either activate or deactivate another protein.1304

CDKs/Cyclin-dependent kinases, the name tells you something about them. They are dependent on cyclins.1310

CDKs are cytoplasmic proteins that are inactive until they are bound to cyclin.1316

Active CDKs give the "go ahead" signal at the restriction point and the other checkpoints.1330

These CDKs are existing in the cytoplasm, and when the cyclin interacts with the CDK, the CDK becomes activated.1338

And when that occurs, it can tell the cell, go ahead to the next part of the cycle.1347

Scientists have done experiments in which they have determined that when the level or the concentration of cyclin increases in the cell, CDK activity also increases.1351

Increased cyclin concentration, the result is increased CDK activity, which makes sense if cyclins are necessary to put CDKs in their active form.1362

When the concentration of cyclins decreases, CDK activity decreases as well.1378

OK, there are other internal and external factors, as well, that regulate the cell cycle.1390

To point out also, the first CDK that was discovered that you should actually know the name of is MPF, and this is known as M-phase promoting factor.1398

This is the "go ahead" signal, gives the go ahead at the G2 checkpoint.1413

Now, CDKs and cyclins are necessary for the cell to go through the cell cycle, but they are not sufficient. There are other factors as well.1422

Even if there is a "go ahead", if there is some other factor that is not correct, the cell may not continue to divide.1432

Internal factors: let me give you an example of an internal factor. An example of an internal factor would be chromosomes lining up, being all lined up correctly at a certain part of mitosis.1441

So, even if the "go ahead" signal is given, everything the cell needs to divide is there, if the chromosomes are not in place, it is not just going to keep going.1453

Internal factors are making sure that everything is in place in the correct order before the cell goes on.1461

Example of an internal factor is cell waits for chromosomes to line up before proceeding with mitosis or miosis. That is an internal factor, something inside the cell.1470

CDKs are internal as well, but they are put in a slightly different class.1488

OK, a second type of factor: external factors. These are things that come from outside the cell, for example, nutrients.1493

Even if the cell gets the "go ahead" signal, if it is in a situation where there is no nutrients, that is probably not a good time to divide1501

because there will not be enough nutrients to support the daughter cells.1507

Growth factors: growth factors are secreted by cells, and they induce other cells to divide.1511

They do not come from within the cell that is going to divide. They come from outside it.1520

One cell secretes a growth factor. This cell secretes a growth factor, and what that is going to do, that growth factor is act on nearby cells and tell them "OK".1524

This is the growth factor, let's say, and it is going to tell this cell over here "divide". That is an external factor.1536

These are factors that tell the cell it is OK to divide. The go ahead signal is given.1543

The internal factors are in place. The external factors are in place, go ahead and divide.1548

Conversely, there are factors which stop cell division.1554

The cell knows that it needs to stop dividing under certain conditions. We talked about if maybe there is not enough nutrients, or the chromosomes are not lined up.1560

But there are other things as well, and two important facts to remember is that there is something called contact inhibition and anchorage dependence.1568

Contact inhibition means that the cell will not divide if the situation is too crowded, so it is inhibited by contact with too many other cells around it.1586

This is also called density-dependent inhibition, and this exists both in the lab in vitro and in a living organism in vivo.1598

If you are working in the lab with cell culture, you will see that the cells will just stop dividing once they reach a certain density.1610

They will not just pile up and pile up, and that is due to contact inhibition.1617

Anchorage dependence means that the cell needs to be attached to a substrate.1620

In the lab, if you are growing cells, the container that you are growing the cells in, the cell is going to attach to.1625

And the cells floating around, will not just be floating around and dividing, they have to be attached.1632

Normal cells exhibit contact inhibition and anchorage dependence meaning that they will not divide if the situation is too crowded.1638

And they will not divide if they are not anchored to something. That is normal cells.1647

Cancer cells lose these controls, so let's talk about cancer cells.1653

First, cancer cells may not necessarily wait for the "go ahead" signal at the checkpoints, so I talked about the "go ahead" signal.1667

They might just plough through and go through the cell cycle and go through it again and not wait to get the "go ahead".1675

That is one way in which cancer cycles do not adhere to the normal regulation of the cell.1681

As I mentioned, they also exhibit a loss of density-dependent inhibition, or this is the same as contact inhibition.1689

Even though they are in a really crowded condition, they will just keep growing.1696

They also lose anchorage-dependence, meaning that they do not need to be attached. They might grow even though they are not attached to a substrate.1701

The result of these various factors is that the cells can form tumors, and cancer, as you know, can also spread.1710

It can spread to nearby sites. It can also spread to distant sites, and this spread to the distant sites of the body is called metastasizing or the cell metastasizes.1721

Metastasis- spread to a distant site.1733

Another thing that cancer cells do is they actually induce blood vessels to grow towards them.1740

So, a tumor will actually somehow induce blood vessels to grow toward it.1747

When that happens, now, those cells have a means to get to other areas of the body, and cancer cells actually use blood vessels and lymphatic vessels to spread.1752

Then, since they do not exhibit anchorage dependence, they do not have to be on a substrate. They will start growing somewhere else in the body.1763

And even if things get crowded, they will still grow, and then, they can spread to areas and damage them.1770

For example, let's say that an individual has breast cancer. She has a tumor in her breast.1776

Some of those cells from the breast cancer can invade bone, so they spread to the bone. They grow there, and can damage the bone and cause fractures.1783

When scientists are studying cancer, one thing that they focus on is how are cancer cells different than normal cells, and here are some ways in which they are different.1793

And later on, when we talk about molecular biology, we will look a little more closely at the molecular level about regulation of genes and how that can affect cancer.1800

Alright, let's do a few examples to reinforce what we have just learned.1816

First of all, example one: label the parts of the chromosome below.1820

What is the complex of DNA and protein of which chromosomes are made called? What is the protein component of this material called?1827

So, parts of the chromosome, well, first of all, I see that there are two sister chromatids here, and each of them has a short arm; and each of them has a long arm.1835

And there are two, there are sister chromatids, so we can label those "sister chromatids".1854

Remember that sister chromatids are connected by what is called a centromere.1866

We have the short arm, the long arm, sister chromatids attached by a centromere.1874

What is the complex of DNA and protein of which chromosomes are made called? What is a chromosome made out of?1881

It is made out of chromatin.1887

What is the protein component of this material called? Remember, chromatin is made of DNA and protein.1893

What is this protein? It is histone protein. Histone proteins plus DNA equals chromatin, and that is what a chromosome is composed of.1898

Example two: the figure below shows a schematic representation of the cell cycle with the G1 phase labelled.1911

Label the remaining phases. What phase are non-dividing cells are rested in?1919

Starting out with the G1 phase, which is a growth phase, it is Gap 1, cells that get the "go ahead" will continue on into the S phase.1924

During the S phase, growth continues, and in addition, DNA is replicated, so it is the synthesis phase, S phase or synthesis.1933

The next phase is G2. This is the second gap phase, Gap 2, and during this phase, growth continues.1943

All of these three together are known as interphase. Remember, the cycle spends the vast majority of its time in the interphase, about 90% of the time.1952

Then, the other 10% of the time is spent in M phase, the mitotic phase.1964

Mitotic phase consists of mitosis, which is the separation of the chromosomes into two groups, one for each of the daughter cell nuclei. That is mitosis.1970

Cytokinesis is the physical division of the parent cell into two daughter cells, and remember, in animal cells, that is via a cleavage furrow. In plant cells, it is via the formation of a cell plate.1982

These are the phases.1997

Now, what phase are non-dividing cells are rested in? These cells are in the G0 phase, a quiescent phase, and they are called sometimes post-mitotic cells.2000

Where are the checkpoints in the cell cycle? There are three: G1, S and G2.2015

And remember that G1 is called the restriction point, and if the cell gets the "go ahead" at G1, there is an excellent chance it is going to make it through the whole cell cycle.2023

What are three means by which the cell cycle is regulated? Well, the first one is cytoplasmic factors, and specifically, these cytoplasmic factors are cyclin and cyclin-dependent kinases or CDKs.2034

That is one way, in which a cell cycle is regulated. It is also regulated by internal factors, and the example I gave was the chromosomes lining up.2054

Everything has to be in place in the correct location for the cell cycle to continue.2064

The third type of factors is external factors. External factors include things like nutrients or the presence of growth factors.2070

Remember that there are also ways in which the cell cycle can be stopped, that it can be stopped by contact inhibition, when things become too crowded.2083

It can be stopped by anchorage dependence, so if there is nothing for the cell to hold on to, there is no substrate, it will not continue to divide.2093

Example four: how does the loss of contact inhibition and anchorage dependence allow cancer cells to spread to other areas of the body?2103

OK, contact inhibition, I just mentioned, should stop a cell from dividing, so if things become too crowded, crowded conditions, normal cells stop dividing.2115

Cancer cells do not. Cancer cells can keep dividing in these conditions.2139

Cancer cells may keep dividing. This allows them to form tumors, so even though it has crowded conditions, cell continues to divide.2144

The second one is anchorage dependence. If there is no substrate for the cell to hold on to, normal cells stop dividing.2156

Cancer cells do not. This allows them to break off, go through to blood stream, travel or metastasize or metastasize and grow in distant sites of the body.2173

They do not need the substrate. They can travel through the bloodstream or the lymphatic vessels, set up elsewhere and divide.2205

And this can form tumors and continue to divide even though it is very crowded to the point that it is damaging the organ.2213

The lack of contact inhibition and anchorage dependence allows cancer cells to spread to other areas of the body, metastasize and form tumors.2222

In addition, one thing to know is that a normal cell will only divide a set number of times. It will only go through the cell cycle, let's say 50 times, and then, it will die.2232

Cancer cells sometimes become immortal. They will divide and divide and divide indefinitely, so we call that immortalizing.2243

And that is another reason that tumors form and cancer spreads, is they have an infinite number or a very high number of cell divisions that they can go through unlike normal cells.2251

That concludes this lesson on the cell cycle.2263

I will see you again soon here at Educator.com.2267