62-02-02 Cell Cycle

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Cell growth and division
Dr. Piyapat Pin-on
Objectives
• Describe cell growth and division in eukaryote: mitosis and meiosis.
• Describe molecular mechanism for regulating mitotic events and
checkpoints in cell-cycle regulation.
Learning Objectives
 Explain the problems that growth causes for cells.
 Compare asexual and sexual reproduction.
Limits to Cell Growth
• The larger a cell becomes, the more demands the cell places on its
DNA and the more trouble the cell has moving enough nutrients and
wastes across the cell membrane.
• Two reasons why cell size is limited:
• If a cell were to grow without control, DNA overload
would occur.
• Rate of material exchange is dependent on surface area
http://www.youtube.com/watch?v=xuG4ZZ1GbzI
I.
Cell Growth
A. A living thing grows because it produces more and more cells.
1. The cells of a human adult are no larger than the cells of a
human baby, but there are more of them.
2. The smaller the cell the better it is. The larger the cell the more difficult to
perform cellular functions.
3. Cell division is the process whereby the cell divides into two daughter cells.
Limits to Cell Growth
• As a cell grows larger:
• More demands are put onto the cell’s DNA.
• The cell has more trouble moving enough nutrients and wastes
across the cell membrane.
• A cell’s functions are controlled by its DNA.
• As a cell grows, it usually does not make more
DNA.
• If the cell were to grow continuously, it would
become too large for the DNA to control...this
is called “DNA Overload”.
• Materials such as food, oxygen, waste and
water pass in and out of a cell through the cell
membrane.
• The rate at which materials can pass through
the membrane depends on the cell’s surface
area.
• The rate at which food and oxygen are used
and waste is produced depends on the cell’s
volume.
• To maintain high efficiency, cells maintain a large
surface area to volume ratio.
• Imagining that cells are cube-shaped, look at the
example below:
Which value
increases
most rapidy?
How does
the SA:V
ratio change
as the cell
Cell Division
• Before a cell
becomes too large,
it divides into two
daughter cells by a
process called cell
division.
II. Cell Division
A. The first stage of cellular division in Eukaryotes is called mitosis. The
second stage is called cytokinesis.
B. Chromosomes
1. In Eukaryotic cells, chromosomes carry the genetic information
that is passed on from one generation of cells to the next.
C. The cell cycle
1. The cell cycle describes the life of a Eukaryotic cell.
2. The cell cycle is a repeating sequence of cellular growth and division
during the life of an organism.
3. A cell spends 90% of its time in the first three phases of the cycleInterphase.
4. First growth (G1)phase- a cell grows rapidly and carries out its
routine functions. Cells that are not dividing remain in the G1 phase.
5. Synthesis (S) phase- A cell’s DNA is copied during this phase. At the
end of this phase, each chromosomes consists of two chromatids
attached at the centromere.
6. Second growth (G2) phase-In the G2 phase, preparations are made
for the nucleus to divide.
7. Mitosis- The process during cell division in which the nucleus of a
cell is divided into two nuclei.
8. Cytokinesis- the cytoplasm
splits.
Controls on Cell Division
• Effects of controlled cell growth can be seen by placing some cells in a
petri dish containing nutrient broth
• Cells grow until they form a thin layer covering the bottom of the dish
• Cells stop growing when they come into contact with other cells
• If cells are removed, the remaining cells will begin dividing again
• Something can turn cell division on or off
Regulating Cell Growth
• Cyclins- proteins that regulate the timing of the cell cycle in
eukaryotic cells
• Internal regulators: proteins that respond to events inside the cell
• i.e. make sure all chromosomes have been replicated; make sure all chromosomes are
attached to the spindle before entering anaphase
• External regulators: proteins that respond to events outside the cell
• i.e. embryonic development; wound healing
D. The cell cycle is carefully controlled.
1. If a cell spends 90% of its time in interphase, how do cells “know”
when to divide?
2. Cell Growth (G1) checkpoint-This checkpoint makes the key
decision of when the cell will divide or not.
3. DNA synthesis (G2) checkpoint-DNA replication is checked at this
point by DNA repair enzymes. If this checkpoint is passed, proteins
help to trigger mitosis.
4. Mitosis check point- will trigger the exit from mitosis.
B. Cell cycle regulators.
1. For many years scientists are looking for something that can
regulate the cell cycle.
2. It was discovered that a protein cyclin regulated the cell cycle.
3. Cyclin regulate the timing of the cell cycle in Eukaryotic cells.
4. It was also discovered that there are two types of regulator proteins
1- those that occur inside of the cell and 2- those that occur outside
of the cell.
C. Internal regulators
1. Proteins that respond to events inside the cell are called internal
regulators.
2. Internal regulators that allow the cell cycle to proceed only when
certain processes have happened inside of the cell.
D. External regulators
1.
Proteins that respond to events outside the cell are called
external regulators.
2. External regulators direct ells to speed up or slow down the
cell cycle.
3.
Growth factors are among the most important external
regulators.
4. They stimulate the growth and division of cells.
5. Growth regulators are very important in embryonic
development and wound healing.
Regulating the Cell Cycle
•Experiments show that normal cells will continue to grow
until they come into contact with other cells.
•When cell’s come into contact with other cells, they stop
growing. This is called contact inhibition.
•This demonstrates that cell growth and division can be
turned on and off.
Regulating the Cell Cycle
Learning Objectives
 Describe how the cell cycle is regulated.
 Explain how cancer cells are different from other cells.
The Discovery of Cyclins
• Scientists found a protein in a cell undergoing mitosis.
• They injected the protein into a non-dividing cell.
• A mitotic spindle started to form.
• Cyclins: proteins that regulate the cell cycle
Regulatory Proteins
Internal regulators:
• respond to events inside the cell
• let cell cycle proceed only when
certain steps have already
happened
External regulators:
• respond to events outside the
cell
• direct cells to speed up or slow
down the cell cycle
• growth factors: wound healing
and embryonic development

Cdk (cyclin dependent kinase, adds phosphate to a protein), along with
cyclins, are major control switches for the cell cycle, causing the cell to move
from G1 to S or G2 to M.

MPF (Maturation Promoting Factor) includes the CdK and cyclins that triggers
progression through the cell cycle.

p53 is a protein that functions to block the cell cycle if the DNA is damaged. If
the damage is severe this protein can cause apoptosis (cell death). p53 levels
are increased in damaged cells. This allows time to repair DNA by blocking
the cell cycle.
 A p53 mutation is the most frequent mutation leading to cancer. An
extreme case of this is Li Fraumeni syndrome, where a genetic a defect in
p53 leads to a high frequency of cancer in affected individuals.

p27 is a protein that binds to cyclin and cdk blocking entry into S phase.
Recent research (Nature Medicine 3, 152 (1997)) suggests that breast cancer
prognosis is determined by p27 levels. Reduced levels of p27 predict a poor
outcome for breast cancer patients.
Contact Inhibition
Copyright Pearson Prentice Hall
• Proteins called cyclins regulate the timing of
the cell cycle.
• Internal regulators: allow the cell to proceed
to the next phase of the cell cycle only when
certain processes have occurred inside the
cell.
• Example: These proteins will not allow a cell to
continue into G2until all chromosomes have been
duplicated during S phase.
• External regulators: speed up or slow down the
cell cycle depending on events outside of the
cell.
• Example: Contact inhibition
The Cell-Cycle Control System Depends on
Cyclically Activated
Cyclin-Dependent Protein Kinases (Cdks)
THE CELL-CYCLE CONTROL SYSTEM
Cdk Activity Can Be Suppressed By Inhibitory
Phosphorylation
and Cdk Inhibitor Proteins (CKIs)
Regulated Proteolysis Triggers the Metaphase-toAnaphase
Transition
Cell-Cycle Control Also Depends on
Transcriptional Regulation
The Cell-Cycle Control System Functions as a
Network of Biochemical Switches
Uncontrolled Cell Growth
• Cancer- a disorder in which some of the body’s own cells lose the
ability to control growth.
• Disease of the cell cycle
E. Uncontrolled cell growth.
1.
Why is cell growth regulated so carefully?
2.
Cancer is a consequence of uncontrolled cell growth.
3. Cancer is a disorder in which some of the body’s own cells
lose the ability to control growth
4. Cancer cells do not respond to the signals that regulate the
growth of most cells.
5. As a result, they divide uncontrollably and form masses of cells
called tumors that can damage the surrounding tissues.
6. Cancer cells may break loose from tumors and spread
throughout the body, disrupting normal activities and causing
serious medical problems or even death.
7. There are certain carcinogens that can cause this to happen.
Such as: tobacco, radiation exposure, and even a viral infection.
8. Cancer is a disease of the cell cycle, and conquering cancer
will require a much deeper understanding of the processes that
control cell division.
Uncontrolled Cell Growth
• Cancer is a disorder in which the body’s own
cells lose their ability to respond to signals
from internal and external regulators.
• These cells divide uncontrollably and form
tumors.
Cancer: Uncontrolled Cell Growth
• Cancer cells don’t respond to normal regulatory signals.
• Cell cycle is disrupted.
• Cells grow and divide uncontrollably.
tumor
blood vessel
Cancer Formation: A Closer Look
1. A cell begins to divide
abnormally.
2. Cells produce a tumor and start
to displace normal cells and
tissues.
3. Cancer cells move to other parts
of the body.
What Causes Cancer?
In all cancers, control over
down.
the cell cycle
has broken
Cancer results from a defect in genes that control cell growth and
division.
Treatments for Cancer
• Surgery to remove localized tumor
• Radiation to destroy cancer cell DNA
• Chemotherapy to kill cancer cells or slow their growth
The Process of Cell Division
Learning Objectives
 Describe the role of chromosomes in cell division.
 Name the main events of the cell cycle.
 Describe what happens during the four phases of
mitosis.
 Describe the process of cytokinesis.
The structure of a chromosome
• Chromatin
• Chromatid
• Centromere
• Chromosomes are not visible in most cells except during cell division.
• At the beginning of cell division the chromosomes condense into
compact, visible structures that can be seen under a light microscope.
The Chromosome
• Chromosome: “X” shaped cell structure
that directs cell activities and passes on
traits to new cells.
• Each identical strand of the
chromosome is called a chromatid.
• The strands are held together by a
structure called the centromere.
• Chromatin: Loosely coiled DNA
Parts of a Chromosome
The Cell Cycle
• Interphase
• G1 Phase: Cell Growth
• S Phase: DNA Replication
• G2 Phase: Preparation for Mitosis
• Prophase
• Metaphase
• Anaphase
• Telophase
• Cytokinesis
Interphase: G1
• Cell Grows
• Synthesis of proteins and new
organelles
S-Phase
• Chromosomes are duplicated and
the synthesis of DNA molecules
takes place.
G2 Phase
• Many of the organelles and
molecules required for cell
division are produced.
• The cell is then ready to enter MPhase to begin the process of Cell
division
Interphase
• 3 phases
• G1 phase= cells do most of
their growing
• Increase in size and
synthesize new proteins and
organelles
• S phase= chromosomes are replicated and the synthesis and DNA
molecules takes place
• Usually if a cell enters S phase and begins replication, it completes the rest
of the cycle
• G2 phase= many of the organelles and molecules required for cell
division are produced
• Shortest of the 3 phases of interphase
Mitosis
• Divided into 4 phases
•
•
•
•
Prophase
Metaphase
Anaphase
Telophase
• Followed with Cytokinesis
• Depending on cell- may last a few minutes to several days
The Principle Stages of M Phase (Mitosis and
Cytokinesis) in an Animal Cell
Prophase
• The chromatin condense into
chromosomes.
• The centrioles separate and a
spindle begins to form.
• The nuclear membrane breaks
down.
Prophase
• 1st and longest phase
of mitosis
• Events
• Chromosomes become visible
• Centrioles separate and move to opposite sides of the cell
• Chromosomes become attached to fibers in the spindle at
the centromere
• Chromosomes coil more tightly
• Nucleolus disappears
• Nuclear envelope breaks down
Prophase
• First and longest phase of
Mitosis.
Spindle
forming
• Chromosomes condense and
become visible.
• Centrioles move to opposite
sides of the nucleus.
• Spindle appears.
• Nucleolus disappears.
Centromere
Chromoso
mes
(paired
Prophase
The nucleus condenses and chromosomes become visible. The
spindle begins to form.
Metaphase
• The chromosomes line up
along the middle of the
cell.
• “M”eet
in the
“M”iddle!
• Each chromosome is
connected to a spindle
fiber at its centromere.
Metaphase
• Often lasts only a few
minutes
• Events
• Chromosomes line up
across the center of
the cell
• Microtubules connect
the centromere of
each chromosome to
the two poles of the
spindle
• Chromosomes are made up of DNA and protein.
• Before prophase, they are not visible because
their thin strands are spread throughout the
nucleus.
• During S phase, the chromosomes are
replicated.
• Once replication has occurred, each chromosome
consists of 2 “sister” chromatids, which are held
together at a centromere.
Metaphase
Centriole
• Second phase of mitosis.
• Chromosomes line up
across the center of the
cell.
• Spindles attach to the
centromere of each
chromosome, connecting
them to the centrioles
and holding them in
place.
Spindle
Metaphase
Chromosomes line up at the center of the cell.
chromati
d
centriole
s
centrom
ere
chromos
ome
Anaphase
• The sister chromatids separate
into individual chromosomes and
move apart.
• Anaphase pulled Apart
Anaphase
• Centromeres split
• Sister chromatids separate
and move to opposite poles
• Anaphase ends when
chromosomes stop moving
Anaphase
• Third phase of mitosis.
• The centromeres split
allowing the sister
chromatids to separate.
• Spindles pull the sister
chromatids to opposite
sides of the cell.
Individual
chromosomes
Anaphase
Chromosomes move toward opposite poles.
individual
chromosomes
Telophase
• The chromosomes gather
at opposite ends of the
cell and lose their distinct
shapes.
• Two new nuclear
membranes form
• Two new Nuclei
Telophase
• Chromosomes begin to
disperse into a chromatin
• Nuclear envelope re-forms
around each cluster of
chromosomes
• Spindle begins to break
apart
• Nucleolus becomes visible
Telophase
• Final phase of Mitosis.
• Chromosomes unravel
• Nuclear envelopes reform
• Nucleolus reappears
• Spindle begins to break
apart.
Telophase
The cell begins to divide into daughter cells.
nuclear envelopes
re-forming
Cytokinesis
• The cell membrane
pinches the cytoplasm in
half.
• Each daughter cell has an
identical set of
duplicate chromosomes.
Cytokinesis
• Occurs at the same time as
telophase
• Animal cells:
• Cell membrane is drawn inward until
the cytoplasm is pinched into 2 nearly
equal parts
• Plant cells:
• Cell plate forms midway between the
divided nuclei
• Cell wall begins to appear in the cell
plate
• Result? 2 new identical cells
Cytokinesis
• Mitosis is considered to be the division of the
nucleus.
• After mitosis, two nuclei with identical sets of
chromosomes are present within the cytoplasm
of a single cell.
• Cytokinesis is the division of the cytoplasm,
which completes M Phase of the cell cycle.
Cytokinesis
• Usually occurs simultaneously with telophase.
• In animal cells:
• The cell membrane is pulled inward until the
cytoplasm is pinched in equal parts.
• In plant cells:
• A “cell plate” forms midway between the two new
nuclei. The plate will eventually develop into a cell
wall dividing the two cells.
Cytokinesis
In animal cells, the cell membrane pinches in the center to form
two daughter cells.
Length of the Cell Cycle of a Human Liver Cell
• Interphase: 21 hours
• Growth : 9 hours
• DNA Replication: 10 hours
• Preparation for Division: 2 hours
• Mitosis: 1 hour
•
•
•
•
Prophase
Metaphase
Anaphase
Telophase
Sexual Reproduction
• Sexual reproduction involves the
parent cells.
fusion
of two separate
• Offspring inherit some genetic information from each parent.
Comparing Asexual and Sexual Reproduction
Asexual
 Produce many offspring in
short period
 Don’t need to find a mate
 In stable environments,
genetically identical offspring
thrive.
 If conditions change, offspring
not well adapted.
Sexual
 Relatively fewer offspring;
growth takes more time
 Need to find a mate
 In changing environments,
genetic diversity can be
beneficial.
 Offspring may be less well
adapted to current conditions.
Homolog Segregation Depends on Several Unique
Features of
Meiosis I
CONTROL OF CELL DIVISION AND CELL
GROWTH
Mitogens Stimulate G1-Cdk and G1/S-Cdk
Activities
Cells Can Enter a Specialized Nondividing
State
Cell Proliferation is Accompanied by Cell
Growth
Proliferating Cells Usually Coordinate Their
Growth and Division
Learning Check
• Name the main events of the cell cycle.
• What happens during each stage of interphase?
• What are chromosomes made of?
• At the completion of M Phase (Mitosis and
Cytokinesis), two identical daughter cells have
formed.
• These two daughter cells restart the cell cycle
at G1 of interphase.
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