Biology 1A - Lecture 12: Cell Cycle




Uploaded by UCBerkeley on 21.09.2012

Transcript:
>>INSTRUCTOR: Good morning. Good morning. I would like to get started.
So in case you have missed it on Monday's exam, it starts at 8:00ハa.m., please be
there on time, for your own sake so you have more time to answer the questions.
Please go to the correct room, you will be in 6 different rooms.
Because this room doesn't hold everybody and we want to make sure that you are not too
intimidated by the elbows of your neighbors. Okay.
So you need to split up into 6 different rooms and please go depending on your discussion
section to your assigned location, you find that on bSpace where you have to go.
Please note that if you go to the wrong room, it's very likely that you won't be able to
get an exam. Because we didn't make excessive copies of the exam, so please look on bSpace
which discussion section you are and then go to your assigned room. On Monday and Tuesdays
there will be no discussion, so whoever have discussion Monday Tuesday, you luck out because
we don't have it. So today we completelyハ we leave the molecules
behind and we move towards the cell again, cell biology.
This lecture will be part of the midterm on Monday.
There will be 4 or 5 questions from today's lecture.
But it's easy so don't worry about it, so we're going discuss mitosis and cell division
today. Cell division the ability of a cell to divide
and propagate is one of the unique aspects of life without division there wouldn't be
life, if you have a unicellular organism and divide it you have a new organism, you have
a multicellular organic it can grow. So it's an aspect of life. So before we start, I have
a movie. [Laughter].
So, and now can you please switch. Okay, the upper one's switched.
Oh, that's okay. So I'm going to show the movie twice, I'm
going to show you the movie for the first time so you get a feel of what we're going
to discuss today and I'm going to show you the movie again, towards the end of the lecture
because you should have understood what the movie shows. You're going do special effects
again. Okay.
Let's see. [VIDEO]
>>INSTRUCTOR: Oh, wrong one. Wrong position.
[VIDEO] Okay.
[Applause]. Movie, what movie was that?
Where are the fan girls and fan boys? Iron Man 2.
Okay. Was a little difficult I know.
Okay. So that's what you to look forward to today.
Now we see already, soハ cell division is part of what is called: The cell cycle.
And the cell cycle is put together into phases. The most dominant phase is the interphase,
so in the interphase, in the interphase you have the G 1 phase that's the gap 1, that
is followed by the S 1, the synthesize phase that's where DNA is replicated and you get
two strands of DNA, that is followed by another gap, the gap 2, and then finally, we get to
mitosis where the chromosomes are split and the cell divides.
So you have here, the second phase is the mitotic phase that consists of mitosis the separation of
the chromosomes and the cytokinesis, which is the separation of the cells.
So before we start a little bit of vocabulary to make sure that we talk in the same language.
So cell division, resolves in genetic identical [Indiscernible] cells. There is one exception
and that's meiosis and that you will hear about on Wednesday. So you do not need to
think about meiosis so far. And that's the formation of the gametes the
sperm and the X cells so we're only talking about the genetically identical [Indiscernible]
cells. So in the cell you have a genome. The genome is the entire DNA in a cell. Independent
of how many molecules there are. Yeah, so it's the entire DNA in a cell so,
if you have a prokaryote that has a circular DNA, so it has a single DNA, that would be
the genome, and for us, for us humans in a regular, say skin cell we have 46 chromosomes
that that should be the entire genome. Now the DNA molecules are packed into the chromosomes
and the definition of a chromosomes is single DNA molecule.
Okay so, again in the prokaryote, you 1 molecule, so that would be it and then the in the eukaryote
you have multiple chromosomes that each have one 1 DNA molecule.
Now the chromosomes the DNA is not alone it can be packed with proteins and that is called
chromatin. Now, you two types of cells in your body,
they are the somatic cells these are the non reproductive cells, liver, skin, muscle, whatnot,
they usually have chromosomes number of 2N so they're deployed and they have two copies
of each chromosomes. And then you the gametes, the gametes are
the sperm and the [Indiscernible] egg cell and they only have a single copy of your DNA.
>>STUDENT: [Indiscernible] >>INSTRUCTOR: Good question, no it does not.
Usually, the genome is nuclei. So no now what you see down here is the condensed form of
a chromosome, actually these are two copies of the same chromosomes they're attached by
what is called the centromere. And so each of these halves are called sister chromatids,
so these are exact copies of each other. And you will see where they come in.
So, if we talk about mitosis that is a separation of chromosomes here, you have a chromosomes
with is a centromere, these arms are called chromosomes arms so you have a single DNA
molecule on a molecular level so what you have a duplication.
And the duplication of the chromosomes happens in the S phase that was in the S phase of
the cell cycle. And what you get then are sister chromatids so you have two identical
copies of that chromosomes. And then during mitosis, these two sister chromatids separate
and form two new cells and as you can see that each cell again has a single copy and
that's the M phase of the cell cycle. Now, in order for these sister chromatids
to separate, there is a very elaborate mechanism, and that involves the mitotic spindle.
So, the mitotic spindle is consists of microtubules, so remember we had that this the cytoskeleton
sections, these are the hollow tubes that have the plus and the minus end and they have
a protein monomers that add on. So these microtubules form this mitotic spindle and they form from
the centrosomes, you see here two centrosomes, they will duplicate, and you have two centrosomes,
that's not officially part of mitosis that naps the interphase before mitosis. And then
these centrosomes, two centrosomes and each have two centrioles these two perpendicular
thing, each of them have two centrioles, they move to different sides of the cell and they
exude the microtubules. Now, there are two times of microtubules,
one are the microtubules that overlap here, and they just make sure that this system is
stable. And then you microtubules that connect to
the chromosomes here. And they connect to this protein that sits
at the centromere of the chromosomes and that is called the kinetochore, I don't know how
you pronounce it in English, kinetochore, no, what? Kinetochore, okay. So it's the kinetochore.
So that's where the microtubules link to the chromosomes and then these microtubules can
move the chromosomes around. Yeah?
And so they do this, here, again, here you see a cell, you see the chromosomes and here
in these gray filaments that the microtubules, and so what we have here on one end are the
centrosomes. So, in an early phase the microtubules will
bind to the kinetochore, they will wiggle and ever ever around the chromosomes will
split in a later phase and then they will be pulled away from one side and they have
found out how the pulling mechanism works here you have a chromosomes, here you have
the protein complex, the kinetochore, here you the microtubal and it turns out there
is are multiple proteins that move the chromosomes the kinetochore, and then they're degraded
from the middle, basically, yeah, so this thing moves here, and the microtubules are
not degraded from here they're degraded from the inside and they're degraded out while
the chromosomes is moved to one direction. So here are then the five phases of mitosis
and you should know these five phases. Here is the gap two phase of the interphase
that's before mitosis. The centrosomes have duplicated already.
Here you have the nucleus, you have the nuclear envelope, so everything is still function
and so in the first phase called the prophase, in the prophase the chromosomes condense,
they're going to get bundled up with proteins so, they condense, and then suddenly they
become visible, so you will have thatハ you will see chromosomes basically, at the same
time the early mitotic spindle is generate and you see the two centromeres start, centrosomes
start to move towards the sides. And then you are the next phase, the prometaphase
and then the mitotic phase is completed you the centrosomes on opposite sides of the cell,
and the microtubules are connected to the centrosomes of the now very condensed chromosomes
and they can now move them around. And then you the metaphase and the metaphase
describes that one event where all of the chromosomes are aligned perpendicular to the
two poles of the new cells and then we have the anaphase, where the centrosomes, the centromeres
splits and the two sister chromatids are pulled away, are pulled apart, and then in the telophase,
the chromatids have been pulled apart and so they de condense, so they de convolute
again and the nuclear envelope is formed. And you have what's called cytokinesis that's
when the cell separates so here in animal cells you what is called a cleavage furrow
this is done by another cytoskeleton actin and this actin forms a ring and close it is
ring and then there pinches in the plasma membrane of the cell until you then have two
cells. So, telophase and cytokinesis happen they're
overlapping so the telophase says you have a de condensation of the chromosomes and you
have a new the knew clear envelope forming and of course the mitotic spindle apparatus
is degraded because it becomes superfluous. One word so the kinesis.
So the separation actually of the cell, that is different in animals and in plant cells.
So in animal cells, you what is called: The cleavage furrow.
And you can see they form a contract tile ring of microfilaments that's actin that pinch
it is cell together until you have daughter cells. Many of the plant cell that happens
differently, the mitosis is actually very similar, here you have see already you have
two different cells in terms of nuclei you have two nuclei here, what they do is they
form a cell plate. So during cell plate formation, you have that
the golgi vesicles, secretes vesicles as I usually does but they're joined in the middle
here and they form the cell plate and eventually the cell plate merges with the cell wall of
the old cell, and then the cell division is complete.
Yeah? So where as in animals you the furrow, which is solely based on cytoskeleton, in
plant cells it's actually based on cell wall synthesis they make this cell wall that eventually
merges, difference between plants and animals. So now I show you the five phases again and
this time in real life, so this is microscopic image. And let's see if this works, so see
here now in the prophase, the chromosomes condense, you still can see the knew clear
membrane, now identity gone so we go to prometaphase, the microtubules have connected to the centromeres,
now they're wiggle the chromosomes around, we have fill in prometaphase until they're
aligned perpendicular to the cell, that takes some time. There it was, and now we have anaphase
where the chromosomes are pulledハ the chromatids are pulled apart and then you the telophase,
and the cytokinesis where the cell separate and where the chromosomes de condense and
where you get nuclear envelope. So we discussed was in the cell cycle you have a gap 1 phase, you a DNA duplication. It's
not part of the mitotic phase and then you have a gap 2 and then you is mitotic phase,
the prophase, where the spindle apparatus starts to build, where the chromosomes start
to condense, you a prometaphase, where the knew clear membrane is integrated where the
microtubules bind to the centromeres you the metaphase where the centハ where the chromosomes
are all aligned perpendicular to the poles you the anaphase where they're pulled apart
into each daughter cell and then you have telophase where the chromosomes de condense
again where new nuclear envelope is formed and then you have cytokinesis where you have
the furrow where the cells are pinched off, okay that's what you need to know. I'm going
to show you the movie again and you should know what it shows.
[VIDEO] >>INSTRUCTOR: This time a little different
music. That DNA duplication.
[Indiscernible]. Now comes the condensation in the prophases,
spindle apparatus develops. Condensation.
Nuclear membrane [Indiscernible] (Music drowning out professor's voice).
And then you have the telophase, de condensation, the nuclear membrane and [Indiscernible] the
cell separate. All right.
Okay. Clear?
Any questions to this? Yes, please?
>>STUDENT: [Indiscernible] >>INSTRUCTOR: In prometaphase.
Actually, in pre prophaseハ what is it called? Prometaphase, yes, you're right.
Prometaphase. Yes. So metaphase is when they're aligned.
So it's actually the shortest phase of it all it's when they aligned, and anaphase already
kicks in. Yes?
>>STUDENT: [Indiscernible] >>INSTRUCTOR: So the question is: The mitotic
spindle apparatus is completely consistent of microtubules. And they go from the centrosomes
to the kinetochore but the microtubules that do not bind to the chromosomes so they keep
the whole apparatus in tact. >>STUDENT: [Indiscernible]
>>INSTRUCTOR: In the movie? The yellow things that were in the centromeres were the kinetochore.
>>STUDENT: [Indiscernible] >>INSTRUCTOR: Oh, the yellow things that form
and condense, these are proteins, they're simple proteins that make sure that the DNA's
properly packed. Hm hmm.
Yes? >>STUDENT: [Indiscernible]
>>INSTRUCTOR: The kinetochore is a protein complex with the microtubules dock onto, a
centromere is where the two chromatids are where they're attached to each other they're
both made out of proteins, centromeres is a region in the chromatids are attached to
each other. Yes?
>>STUDENT: [Indiscernible] >>INSTRUCTOR: The microfilaments of the spindle apparatus the
pinching or the microtubules? Both of them are degraded, basically.
Yes? >>STUDENT: [Indiscernible]
>>INSTRUCTOR: The nucleus, so the nucleus where the ribosomes will make so it will be
condense as well. So nucleolus will condense onto they're representative chromosomes so
there's no distinction between nucleolus or not but once they de condense after anaphase
after cytokinesis they will align together and you will see a new nucleolus forming.
Okay. >>STUDENT: [Indiscernible]
>>INSTRUCTOR: Say it again? The areas that encode the rRNA for ribosomes to form the
nucleolus. That's mitosis require energy? You bet. So
as you can see you have to make the apparatus, you to make sure that everything works with
you to put the proteins in to make sure that the chromosomes condense correctly it requires
a lot of energy, yes. >>STUDENT: [Indiscernible]
>>INSTRUCTOR: So, quiz. Last question.
Question No.ハ15. So if you don't have your 12 points that's
your last chance to make up for the 12 points. So (Reading).
So that was one of the questions I had on the exam and I decided I had too many questions
so I took it out. But still you should be able to answer.
To [Indiscernible] disrupts microtubal formation, so it affects what in cell division? The S
phase, anaphase, the chromatid assembly... (Reading).
You go. Okay. 10 more seconds.
3, 2, 1. All right.
And most of your click answer E, that is correct. So, why is it correct?
So the S phase is gene duplication, no microtubules involved, in the anaphase the microtubules
are actually involved but the problem is if you don't have a mitotic spindle you won't
get there, so the mitotic spindle is affected so everything stops. The chromatid assembly
requires these proteins so it doesn't require microtubules the disassembly of the nuclear
membrane doesn't have anything to do it and so it's the formation of the whole apparatus
that guides through the system. So, even though this was the last question,
what we're going to discuss now is still relevant for the exam.
Right. So, how does the cell control the cell cycle?
Now we come to the interesting bits of this whole thing.
So, what people have done, what scientists have done is they have done cell fusion experiments.
So what that is they took cells and they cultured them and then they went through the various
change stages of the cell cycles and they put the cell together and then they merge,
the plasma membranes merge and you can see how one of the cells changed its behavior
and pretty much immediately. And that told them that there was some sort of signal that's
sitting in the cytosol that moves to the other cell and moves that other cell into a different
stage. And so for example, here, you have a cell
that's in the S phase, so the DNA is duplicated, here you a cell where the DNA is not duplicated
yet, so it's the G 1, the gap 1 phase and if the two are merged the gap 1 phase moves
immediately to the S phase and the DNA gets immediately duplicated.
Here is another experiment, where one of the cells was in the M phase, so you see already
the mitotic spindle is already coming up, and you already the duplication is done the
chromosomes are condensed if you put together with a G 1 cell so the DNA is not duplicated
yet you put them together the G 1 cell will immediately move to the mitotic phase, even
though it does not have had gene duplication yet.
So it will jump over S and G 2 and move immediately to M, you see that here too. Here you have
one chromatid and here you have two. It will still jump overハbecause they're cytosolic
components that move from this cell and this cell and induce with mitosis.
So the way you should think of this cell cycle is that it's like it's a washing machine,
that's what the book says and it has control check points here. So for example, it has
a check point in the G 1 and if a signal is there, the check point can turn to green and
it moves onto the S phase, if you don't have in molecule there, the cell will reside in
the G 1 phase. In fact it might move to the G 0 phase, the G 0 is a nondividing cell state
so it's a parking position, basically, the cell will move there and with will not divide
anymore and that happens for example to your nerve cells they cannot divide anymore they're
parked in G 0. Your liver cells are sometimes also parked
in G 0, but they can be sort of redirected so liver cells in particular signals come
along, that signal can move and liver cells can move out of G 0, move to S G 2 and divide
again. Yeah, nerve cells cannot do that, nerve cells
once they reach G 0 that's the end they're going to stay there as such.
And so the question then is, what are these molecules that flip over the signal?
At these check points? So there's one at the G 1 phase, and there is one after the G 2
phase that starts the mitosis and there's one in the middle of mitosis to make sure
that the mitosis works properly. So, one of the signals that is important for
the G 2, check point, here, the G 2 check point is a molecule protein called cyclin.
Or cyclin. So cyclin is a protein that oscillates in
its concentration. So you have here various cell cycles and in purple you the cyclic concentration
in your cell and you can see in the S phase and in the G 2 phase in particular, the cyclin
concentration goes tremendously up and in the M phase it's completely degraded.
And then it stays at the low level and when the S phase comes along it starts to increase
again in the G 2, gets very high and when the M phase comes it goes down again.
So it is one of these oscillating proteins that tells the cell in what concern am I in
now. What part of the cycle am I in now? Now the sickle can do anything, the cyclin have
to form a complex where the cyclin dependent kinase and these two, the cyclin + the cyclin
dependent kinase form this maturation promotion factor here. So these two bound together form
the MPF so it's cyclin CDK complex. Now, the kinase, we learn that kinase before, a kinase
is an enzyme that puts a phosphate onto a substrate. Yeah we have for hexokinases in
glycolysis, where it accept a phosphate from ATP, so these kinase take phosphates and move
it to certain proteins in this case. And so what cyclin dependent kinase can do
if it's in complex with the cyclin as an MPF it can phosphorylate proteins on the nuclear
membrane and when these proteins are phosphorylated and then the [Indiscernible] machinery comes
down and breaks down the whole nucleus. So that he is on a example. Now the cyclin dependent
kinase they're in the cell at a constant level, so they do not CDK, they do not oscillate.
Yeah, they stay at a constant level, but what happens as the cyclin accumulates, in the
S and in the G 2, only then they can actually form the complex because you enough cyclin
to form this complex, and so when that complex is there you pass the G 2 check point and
mitosis occurs and after mitosis is done the cyclin is degraded and can't do anything anymore.
And one example of what this kinase does it phosphorylates certain proteins to make sure
that the centrosomes separate that the nuclear membrane is degraded, etc., so this is a good
example of a check point where you have two molecules that interact, one is cyclic and
one is constant, but for this to take effect you need to form a complex ofハboth of them.
So, that was an internal factor. That was the cytosolic signal that I talked about when
I talked about this experiment before so that was in internal factors but there are external
factors and these are growth factors so here if you take a tissue, you cut it into cells
you remove the extracellular matrix so you have single cells and you put it in a flask
and then you put the flaskハ you dump the solution into one of these trays and if you
put a growth factor in there, these cells will divide, and they will cover the entire
bottom of the flask. And so these are called growth factors in
this case its platelet derived growth factor. So you need this growth factor for these cells
to divide. If you let them sit in solution they will
not necessarily divide, you need this external growth factor.
Another two external factors that affect cell division are the Anchorage and the density
dependence. So the Anchorage dependence is that the cells
will only divide if the cells are stuck to a surface.
So again if you have them in a flask and shake them they will not divide, they need to be
able to anchor somewhere and then they will divide.
The density dependence on growth is that once the bottom of that flask is completely covered,
the cells will stop dividing. They will not continue to grow, they will
just cover the surface and then they will stop. And the reason why thisハ how this
works is is that cell A connects to cell B and that gives the signal to stop dividing
so when they touch each other they will stop dividing.
So you can see in this experiment if they have the cells they cover the floor of this
tray, if youハ they will stop dividing but if you remove some and then you leave a gap
and the surrounding cells will start dividing again until that gap is filled. So these density
inhibition because if the density is too large they will stop dividing.
And so with this we get to cancer, because in cancer the whole cell division is turn
array and there's a lot of problems with this. Yes?
>>STUDENT: [Indiscernible] >>INSTRUCTOR: So, the question was, if all
cells need the growth factors, the Anchorage and the density dependence? In general, I
do not know, because I'm a plant guy I'm not an animal guy, I can't imagine many of them
do but some of them don't. All three that they need all three of those.
Hm hmm. But I really don't know. So, in cancer you have the problem that cell
division is uncontrolled. And so for example, here you one cell that
continued to divide and forms a tumor. And so if the tumor remains in that tissue,
and just stay there is, and then it can be called a benign tumor because it doesn't spread.
But then sometimes the cells separate out of the tumor and they go through the blood
vessel of the lymph system they go some other place in your body and they're going to divide
even further and then you have what is called: The metastatic tumor, so if you have a metastasis
of cancer cells that means the original tumor has [Indiscernible] and continues to divide.
And the reason this can divide its immortal it divides and divide and divides.
Is that it produces its own growth factor, so it doesn't need the external factor anymore.
It can produce its own factor, the check points the 3 check points in the cell cycle become
ineffective, so it doesn't see these check points there's no stop sign anymore it just
goes through the cycle around and around and around. And the density and the anchor dependency
are gone. So for example here, again you the tray with the cell, this is a normal cell
in the cancer cell they were just continue to grow and fill up the whole flask, because
that type of inhibition is gone and I think it depends on the type of tumor, which of
these three is obliviated and leads to continue cell cycle it doesn't have to be all three
of those, It can be one or two or all three of those. It depends on the type of cancer
that you have. >>STUDENT: [Indiscernible]
>>INSTRUCTOR: Say it again? They're called growth factors.
So there are many growth factors but they're call growth factors they're proteins, they
exogenous proteins that attach to a cell. Okay. So much for the eukaryotes.
And so we finish with the cell division in bacteria. In the prokaryotes. So they have
a very different mechanism of how the cells are divided.
So in bacteria, this process is called: Binary fission.
And so in the binary fission you a prokaryote here depicted here with a plasma membrane
in a cell wall and it grows approximately to the double size, they don't have multiple
chromosomes they have a circular DNA there is one part of the chromosomes that is called
origin of replication. Origin of replication.
This is a specific segment on the chromosomes and that's where the chromosomes duplicate.
You see here, it forms this bulb, that's where theハ where you make two copies of the chromosomes
at the origin of replication. And then it is attached to the membrane via protein and
then it is pulled apart into the different directions of the cell. And you see this here,
you see one origin moves to the one side of the cell, the other moves to this side of
the cell. So these two daughter DNA molecules are separated, by the origin, so you don't
have a mitotic spindle here, at all, actually. And then the plasma membrane eventually pinches
inward and the cell was is generate and that's how you create two E.ハcoli cells or two
bacteria cells. So you don't have the mitotic spindle you
don't have a nucleus in the first place you don't really have the condensation of the
[Indiscernible] but you have one origin of replication and that's how the chromosomes
are separated. Any questions?
Yes? >>STUDENT: [Indiscernible]
>>INSTRUCTOR: What do the organelles do during cell division? They just happen to be around.
Really. So when the cell divides and the cytokinesis
occurs the pinching it's one on side there than be a few mitochondria, on the other side
there happen to be a few mitochondria. >>STUDENT: [Indiscernible]
>>INSTRUCTOR: I don't think so, I think the prokaryotes don't have the actin ring to pull
it together. Hm hmm. Yes?
>>STUDENT: [Indiscernible] >>INSTRUCTOR: Is there a case where one said
doesn't get a mitochondria? I think it would die.
And therefore the cell would be gone, so I don't think so.
So it cannot reallyハ so if a cell have a mitochondria it cannot provide the energy
and therefore it would die, so therefore it would be gone.
Right at birth, so to say, so I don't thinkハ so what you have to see they're not just like
the two mitochondria in there they're hundreds of mitochondria in there, so the chance that
it happens to be that one doesn't get one, I think are very slim.
Okay. Yes?
>>STUDENT: [Indiscernible] >>INSTRUCTOR: Yes.
Correct. So the Mハ the M checker points, they might stop doing it, yes they might stop
it. So one example of this is for example in plants, plants you get a duplication of
the chromosomes, so they go through half of mitosis but they never do the cytokinesis.
So they stop in the middle and then they stop there.
It happens. Yes. And it happens on purpose. Because then the cell can be bigger, but because
they have multiple copies of their chromosomes. So it happens.
Yes? >>STUDENT: [Indiscernible]
>>INSTRUCTOR: Is there a difference between G 1 and G 2, yes in G 2 you have two copies
of your chromosomes in G 1 you don't, in G 1 you only have a single copy, what happens
in these two phases? The cell lives on there's nothing really related to cell division in
both phases. Last question? >>STUDENT: [Indiscernible]
>>INSTRUCTOR: No, so you do not need to know the specificハ because we didn't discuss
it you do not need to know how G 1 check point and M check point work.
I just wanted to tell they are checkpoints and one we happen to discuss in detail because
of the timing of the class. Okay. All right and that was my task I'm done.
[Applause]. So, thank you.
So it has been a privilege to teaching you the molecules of life, I hope you understand
that the molecules are important, that's how it works anyway, if you want to know more
about it look forward to your biochemical class you been an excellent audience and thank
you very much. ハ