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Chapter 12
The Cell Cycle
PowerPoint Lectures for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Overview: The Key Roles of Cell Division
• The ability of organisms to reproduce best
distinguishes living things from nonliving matter
• The continuity of life is based upon the
reproduction of cells, or cell division
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In unicellular organisms, division of one cell
reproduces the entire organism
• Multicellular organisms depend on cell division for:
– Development from a fertilized cell
– Growth
– Repair
• Cell division is an integral part of the cell cycle, the
life of a cell from formation to its own division
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LE 12-2
100 µm
Reproduction
200 µm
Growth and development
20 µm
Tissue renewal
Concept 12.1: Cell division results in genetically
identical daughter cells
• Cells duplicate their genetic material before they
divide, ensuring that each daughter cell receives
an exact copy of the genetic material, DNA
• A dividing cell duplicates its DNA, allocates the
two copies to opposite ends of the cell, and only
then splits into daughter cells
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Cellular Organization of the Genetic Material
• A cell’s endowment of DNA (its genetic
information) is called its genome
• DNA molecules in a cell are packaged into
chromosomes
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Figure • A model for chromosome structure, human
chromosome 4. The 2-nm DNA helix is wound twice
around histone octamers to form 10-nm nucleosomes,
each of which contains 160 bp (80 per turn). These
nucleosomes are then wound in solenoid fashion with
six nucleosomes per turn to form a 30-nm filament. In
this model, the 30-nm filament forms long DNA loops,
each containing about 60,000 bp, which are attached at
their base to the nuclear matrix. Eighteen of these
loops are then wound radially around the
circumference of a single turn to form a miniband unit
of a chromosome. Approximately 10 6 of these
minibands occur in each chromatid of human
chromosome 4 at mitosis.
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• Every eukaryotic species has a characteristic
number of chromosomes in each cell nucleus
• Somatic (nonreproductive) cells have two sets of
chromosomes
• Gametes (reproductive cells: sperm and eggs)
have half as many chromosomes as somatic cells
• Eukaryotic chromosomes consist of chromatin, a
complex of DNA and protein that condenses
during cell division
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LE 12-3
25 µm
Distribution of Chromosomes During Cell Division
• In preparation for cell division, DNA is replicated
and the chromosomes condense
• Each duplicated chromosome has two sister
chromatids, which separate during cell division
• The centromere is the narrow “waist” of the
duplicated chromosome, where the two
chromatids are most closely attached
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LE 12-4
0.5 µm
Chromosome
duplication
(including DNA
synthesis)
Centromere
Sister
chromatids
Separation
of sister
chromatids
Centromeres
Sister chromatids
• Eukaryotic cell division consists of:
– Mitosis, the division of the nucleus
– Cytokinesis, the division of the cytoplasm
• Gametes are produced by a variation of cell
division called meiosis
• Meiosis yields nonidentical daughter cells that
have only one set of chromosomes, half as many
as the parent cell
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Concept 12.2: The mitotic phase alternates with
interphase in the cell cycle
• In 1882, the German anatomist Walther Flemming
developed dyes to observe chromosomes during
mitosis and cytokinesis
• To Flemming, it appeared that the cell simply grew
larger between one cell division and the next
• Now we know that many critical events occur
during this stage in a cell’s life
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Phases of the Cell Cycle
• The cell cycle consists of
– Mitotic (M) phase (mitosis and cytokinesis)
– Interphase (cell growth and copying of
chromosomes in preparation for cell division)
• Interphase (about 90% of the cell cycle) can be
divided into subphases:
– G1 phase (“first gap”)
– S phase (“synthesis”)
– G2 phase (“second gap”)
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LE 12-5
INTERPHASE
G1
S
(DNA synthesis)
G2
• Mitosis is conventionally divided into five phases:
– Prophase
– Prometaphase
– Metaphase
– Anaphase
– Telophase
• Cytokinesis is well underway by late telophase
[Animations and videos listed on slide following figure]
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 12-6ca
G2 OF INTERPHASE
PROPHASE
PROMETAPHASE
LE 12-6da
METAPHASE
ANAPHASE
TELOPHASE AND CYTOKINESIS
The Mitotic Spindle: A Closer Look
• The mitotic spindle is an apparatus of
microtubules that controls chromosome movement
during mitosis
• Assembly of spindle microtubules begins in the
centrosome, the microtubule organizing center
• The centrosome replicates, forming two
centrosomes that migrate to opposite ends of the
cell, as spindle microtubules grow out from them
• An aster (a radial array of short microtubules)
extends from each centrosome
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• The spindle includes the centrosomes, the spindle
microtubules, and the asters
• Some spindle microtubules attach to the
kinetochores of chromosomes and move the
chromosomes to the metaphase plate
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
fibers of tubulin — called microtubules
— interact with the complex of
proteins known as the kinetochore and
cause the kinetochore to assemble a
ring around these fibers.
Kinetochores are attached to either side of a
chromosome and ferry it along a
microtubule spindle, keeping it segregated
from other chromosomes during cell
division. Segregation is critical for
preventing mistakes that can lead to cancer
and birth defects.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Microtubules
•are straight, hollow cylinders whose wall is made up of a ring of 13
"protofilaments";
•have a diameter of about 25 nm;
•are variable in length but can grow 1000 times as long as they are wide;
•are built by the assembly of dimers of alpha tubulin and beta tubulin;
•are found in both animal and plant cells.
Microtubules
•grow at each end by the polymerization of tubulin dimers (powered by the
hydrolysis of GTP), and
•shrink at each end by the release of tubulin dimers (depolymerization).
However, both processes always occur more rapidly at one end, called the plus
end. The other, less active, end is the minus end.
Microtubules participate in a wide variety of cell activities. Most involve motion.
The motion is provided by protein "motors" that use the energy of ATP to move
along the microtubule.
Microtubule motors
There are two major groups of microtubule motors:
kinesins (most of these move toward the plus end of the microtubules) and
dyneins (which move toward the minus end).
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Direction of motion
Motor proteins travel in a specific direction along a microtubule. This is because the microtubule is
polar and the heads only bind to the microtubule in one orientation, while ATP binding gives each
step its direction through a process known as neck linker zippering.
Most kinesins walk towards the positive end of a microtubule which, in most cells, entails
transporting cargo from the centre of the cell towards the periphery. This form of transport is
known as anterograde transport.
A different type of motor protein known as dyneins, move towards the minus end of the microtubule.
Thus they transport cargo from the periphery (terminal buttons) of the cell towards the centre
(soma). This is known as retrograde transport. Anterograde axoplasmic transport is the faster of
the two transports, moving at a speed of up to 500 mm per day, while retrograde transport moves
about half as fast.
Proposed mechanisms of movement
Kinesin accomplishes transport by "walking" along a microtubule. Two mechanisms have been
proposed to account for this movement.
In the "hand-over-hand" mechanism, the kinesin heads step past one another, alternating the lead
position.
In the "inchworm" mechanism, one kinesin head always leads, moving forward a step before the
trailing head catches up.
Despite some remaining controversy, mounting experimental evidence points towards the hand-overhand mechanism as being more likely.
http://en.wikipedia.org/wiki/Kinesin
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Microtubule motor (kinesin)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 12-7
Aster
Microtubules
Sister
chromatids
Chromosomes
Centrosome
Metaphase
plate
Kinetochores
Overlapping
nonkinetochore
microtubules
Centrosome
1 µm
Kinetochore
microtubules
0.5 µm
• In anaphase, sister chromatids separate and
move along the kinetochore microtubules toward
opposite ends of the cell
• The microtubules shorten by depolymerizing at
their kinetochore ends
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 12-8b
Chromosome
movement
Microtubule
Motor
protein
Chromosome
Kinetochore
Tubulin
subunits
All three groups of spindle fibers participate in
•the assembly of the chromosomes at the metaphase plate at
metaphase. Proposed mechanism (the diagram shows only 1 and 2):
1.Microtubules attached to opposite sides of the dyad shrink or
grow until they are of equal length.
2.Microtubules motors attached to the kinetochores move them
•toward the minus end of shrinking microtubules (a
dynein);
•toward the plus end of lengthening microtubules (a
kinesin).
3.The chromosome arms use a different kinesin to move to the
metaphase plate.
•the separation of the chromosomes at anaphase.
•The sister kinetochores separate and, carrying their attached
chromatid,
•move along the microtubules powered by minus-end motors,
dyneins, while the microtubules themselves shorten (probably
at both ends).
•The overlapping spindle fibers move past each other (pushing
the poles farther apart) powered by plus-end motors, the
"bipolar" kinesins.
•In this way the sister chromatids end up at opposite poles.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Nonkinetochore microtubules from opposite poles
overlap and push against each other, elongating
the cell
• In telophase, genetically identical daughter nuclei
form at opposite ends of the cell
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cytokinesis: A Closer Look
• In animal cells, cytokinesis occurs by a process
known as cleavage, forming a cleavage furrow
• In plant cells, a cell plate forms during cytokinesis
Animation: Cytokinesis
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 12-9a
100 µm
Cleavage furrow
Contractile ring of
microfilaments
Daughter cells
Cleavage of an animal cell (SEM)
Actin is one of the most condensed forms of protein, which is globular and is a monomeric subunit of
microfilament. The thin filaments in actin constitute a major part of it. The formation of thin filaments involves a
complex process involving the activation of G-Actin to ultimately form the ADP-bound Actin. In this case, ATP
acts both as the activator and also the catalyser.
Actin rules over cell functions which include cell division, morphing of the shape of the cells, cell mobility and
other contractile properties. It is a 42 kDa protein and related gene has 100 nucleotides. Functioning of Actin is
generally hindered by introns. Actin filaments are linked to the membrane through vinculin.
Actin basic functions involve:
•Giving mechanical support to cells.
•Enabling easy movement of cellular fluids and hence enhancing cell mobility.
•Participating in signal transmission.
•Working upon the cytoplasm and hardening it.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 12-9b
Vesicles
forming
cell plate
Wall of
parent cell
Cell plate
1 µm
New cell wall
Daughter cells
Cell plate formation in a plant cell (TEM)
LE 12-10
Nucleus
Nucleolus
Chromatin
condensing
Prophase. The
chromatin is condensing.
The nucleolus is
beginning to disappear.
Although not yet visible
in the micrograph, the
mitotic spindle is starting
to form.
Chromosomes
Prometaphase. We
now see discrete
chromosomes; each
consists of two identical
sister chromatids. Later
in prometaphase, the
nuclear envelope will
fragment.
Cell plate
Metaphase. The spindle is
complete, and the
chromosomes, attached
to microtubules at their
kinetochores, are all at
the metaphase plate.
Anaphase. The
chromatids of each
chromosome have
separated, and the
daughter chromosomes
are moving to the ends of
the cell as their
kinetochore microtubules shorten.
10 µm
Telophase. Daughter
nuclei are forming.
Meanwhile, cytokinesis
has started: The cell
plate, which will divide
the cytoplasm in two, is
growing toward the
perimeter of the parent
cell.
Binary Fission
• Prokaryotes (bacteria and archaea) reproduce by
a type of cell division called binary fission
• In binary fission, the chromosome replicates
(beginning at the origin of replication), and the two
daughter chromosomes actively move apart
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 12-11_1
Cell wall
Origin of
replication
Plasma
membrane
E. coli cell
Chromosome
replication begins.
Soon thereafter,
one copy of the origin
moves rapidly toward
the other end of the cell.
Two copies
of origin
Bacterial
chromosome
LE 12-11_2
Cell wall
Origin of
replication
Plasma
membrane
E. coli cell
Chromosome
replication begins.
Soon thereafter,
one copy of the origin
moves rapidly toward
the other end of the cell.
Replication continues.
One copy of the origin
is now at each end of
the cell.
Bacterial
chromosome
Two copies
of origin
Origin
Origin
LE 12-11_3
Cell wall
Origin of
replication
E. coli cell
Chromosome
replication begins.
Soon thereafter,
one copy of the origin
moves rapidly toward
the other end of the cell.
Replication continues.
One copy of the origin
is now at each end of
the cell.
Replication finishes.
The plasma membrane
grows inward, and
new cell wall is
deposited.
Two daughter
cells result.
Plasma
membrane
Bacterial
chromosome
Two copies
of origin
Origin
Origin
The Evolution of Mitosis
• Since prokaryotes evolved before eukaryotes,
mitosis probably evolved from binary fission
• Certain protists exhibit types of cell division that
seem intermediate between binary fission and
mitosis
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 12-12
Bacterial
chromosome
Prokaryotes
Chromosomes
Microtubules
Intact nuclear
envelope
Dinoflagellates
Kinetochore
microtubules
Intact nuclear
envelope
Diatoms
Kinetochore
microtubules
Centrosome
Fragments of
nuclear envelope
Most eukaryotes
Concept 12.3: The cell cycle is regulated by a
molecular control system
• The frequency of cell division varies with the type
of cell
• These cell cycle differences result from regulation
at the molecular level
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Evidence for Cytoplasmic Signals
• The cell cycle appears to be driven by specific
chemical signals present in the cytoplasm
• Some evidence for this hypothesis comes from
experiments in which cultured mammalian cells at
different phases of the cell cycle were fused to
form a single cell with two nuclei
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 12-13
Experiment 1
Experiment 2
S
G1
M
G1
S
S
M
M
When a cell in the S phase was
fused with a cell in G1, the G1
cell immediately entered the
S phase—DNA was synthesized.
When a cell in the M phase
was fused with a cell in G1,
the G1 cell immediately began
mitosis—a spindle formed and
chromatin condensed, even
though the chromosome had
not been duplicated.
The Cell Cycle Control System
• The sequential events of the cell cycle are
directed by a distinct cell cycle control system,
which is similar to a clock
• The clock has specific checkpoints where the cell
cycle stops until a go-ahead signal is received
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 12-14
G1 checkpoint
Control
system
G1
M
M checkpoint
G2 checkpoint
G2
S
• For many cells, the G1 checkpoint seems to be the
most important one
• If a cell receives a go-ahead signal at the G1
checkpoint, it will usually complete the S, G2, and
M phases and divide
• If the cell does not receive the go-ahead signal, it
will exit the cycle, switching into a nondividing
state called the G0 phase
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 12-15
G0
G1 checkpoint
G1
If a cell receives a go-ahead
signal at the G1 checkpoint,
the cell continues on in the
cell cycle.
G1
If a cell does not receive a
go-ahead signal at the G1
checkpoint, the cell exits the
cell cycle and goes into G0, a
nondividing state.
The Cell Cycle Clock: Cyclins and
Cyclin-Dependent Kinases
• Two types of regulatory proteins are involved in
cell cycle control: cyclins and cyclin-dependent
kinases (Cdks)
• The activity of cyclins and Cdks fluctuates
during the cell cycle
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LE 12-16a
M
G1
S
G2
M
G1
S
G2
M
MPF activity
Cyclin
Time
Fluctuation of MPF activity and cyclin concentration
during the cell cycle
LE 12-16b
Cdk
Degraded
cyclin
G2
Cdk
checkpoint
Cyclin is
degraded
MPF
Cyclin
Molecular mechanisms that help regulate the cell cycle
Stop and Go Signs: Internal and External Signals at
the Checkpoints
• An example of an internal signal is that
kinetochores not attached to spindle
microtubules send a molecular signal that
delays anaphase
• Some external signals are growth factors,
proteins released by certain cells that stimulate
other cells to divide
• For example, platelet-derived growth factor
(PDGF) stimulates the division of human
fibroblast cells in culture
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LE 12-17
Scalpels
Petri
plate
Without PDGF
With PDGF
Without PDGF
With PDGF
10 mm
• Another example of external signals is densitydependent inhibition, in which crowded cells stop
dividing
• Most animal cells also exhibit anchorage
dependence, in which they must be attached to a
substratum in order to divide
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LE 12-18a
Cells anchor to dish surface and
divide (anchorage dependence).
When cells have formed a complete
single layer, they stop dividing
(density-dependent inhibition).
If some cells are scraped away, the
remaining cells divide to fill the gap and
then stop (density-dependent inhibition).
Normal mammalian cells
25 µm
• Cancer cells exhibit neither density-dependent
inhibition nor anchorage dependence
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LE 12-18b
Cancer cells do not exhibit
anchorage dependence
or density-dependent inhibition.
25 µm
Cancer cells
Loss of Cell Cycle Controls in Cancer Cells
• Cancer cells do not respond normally to the body’s
control mechanisms
• Cancer cells form tumors, masses of abnormal
cells within otherwise normal tissue
• If abnormal cells remain at the original site, the
lump is called a benign tumor
• Malignant tumors invade surrounding tissues and
can metastasize, exporting cancer cells to other
parts of the body, where they may form secondary
tumors
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LE 12-19
Lymph
vessel
Tumor
Blood
vessel
Glandular
tissue
Cancer cell
A tumor grows from a
single cancer cell.
Cancer cells invade
neighboring tissue.
Cancer cells spread
through lymph and
blood vessels to
other parts of the
body.
Metastatic
tumor
A small percentage
of cancer cells may
survive and establish
a new tumor in another
part of the body.