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CAMPBELL BIOLOGY IN FOCUS
Urry • Cain • Wasserman • Minorsky • Jackson • Reece
9
The Cell Cycle
Lecture Presentations by
Kathleen Fitzpatrick and Nicole Tunbridge
© 2014 Pearson Education, Inc.
Overview: The Key Roles of Cell Division
 The ability of organisms to produce more of their
own kind best distinguishes living things from
nonliving matter
 The continuity of life is based on the reproduction
of cells, or cell division
© 2014 Pearson Education, Inc.
Figure 9.1
© 2014 Pearson Education, Inc.
 In unicellular organisms, division of one cell
reproduces the entire organism
 Cell division enables multicellular eukaryotes to
develop from a single cell and, once fully grown, to
renew, repair, or replace cells as needed
 Cell division is an integral part of the cell cycle, the
life of a cell from formation to its own division
© 2014 Pearson Education, Inc.
Figure 9.2
100 m
200 m
(a) Reproduction
(b) Growth and
development
20 m
(c) Tissue renewal
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Figure 9.2a
100 m
(a) Reproduction
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Figure 9.2b
200 m
(b) Growth and development
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Figure 9.2c
20 m
(c) Tissue renewal
© 2014 Pearson Education, Inc.
Concept 9.1: Most cell division results in
genetically identical daughter cells
 Most cell division results in the distribution of
identical genetic material—DNA—to two daughter
cells
 DNA is passed from one generation of cells to the
next with remarkable fidelity
© 2014 Pearson Education, Inc.
Cellular Organization of the Genetic Material
 All the DNA in a cell constitutes the cell’s genome
 A genome can consist of a single DNA molecule
(common in prokaryotic cells) or a number of DNA
molecules (common in eukaryotic cells)
 DNA molecules in a cell are packaged into
chromosomes
© 2014 Pearson Education, Inc.
Figure 9.3
20 m
Eukaryotic chromosomes
© 2014 Pearson Education, Inc.
 Eukaryotic chromosomes consist of chromatin, a
complex of DNA and protein
 Every eukaryotic species has a characteristic
number of chromosomes in each cell nucleus
 Somatic cells (nonreproductive cells) have two sets
of chromosomes
 Gametes (reproductive cells: sperm and eggs) have
one set of chromosomes
© 2014 Pearson Education, Inc.
Distribution of Chromosomes During Eukaryotic
Cell Division
 In preparation for cell division, DNA is replicated and
the chromosomes condense
 Each duplicated chromosome has two sister
chromatids, joined identical copies of the original
chromosome
 The centromere is where the two chromatids are
most closely attached
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Figure 9.4
Sister
chromatids
Centromere
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0.5 m
 During cell division, the two sister chromatids of each
duplicated chromosome separate and move into two
nuclei
 Once separate, the chromatids are called
chromosomes
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Figure 9.5-1
Chromosomes
1
Chromosomal
DNA molecules
Centromere
Chromosome
arm
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Figure 9.5-2
Chromosomes
1
Chromosomal
DNA molecules
Centromere
Chromosome
arm
Chromosome duplication
2
Sister
chromatids
© 2014 Pearson Education, Inc.
Figure 9.5-3
Chromosomes
1
Chromosomal
DNA molecules
Centromere
Chromosome
arm
Chromosome duplication
2
Sister
chromatids
Separation of sister
chromatids
3
© 2014 Pearson Education, Inc.
 Eukaryotic cell division consists of
 Mitosis, the division of the genetic material in 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
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Concept 9.2: 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
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Phases of the Cell Cycle
 The cell cycle consists of
 Mitotic (M) phase, including mitosis and cytokinesis
 Interphase, including cell growth and copying of
chromosomes in preparation for cell division
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 Interphase (about 90% of the cell cycle) can be
divided into subphases
 G1 phase (“first gap”)
 S phase (“synthesis”)
 G2 phase (“second gap”)
 The cell grows during all three phases, but
chromosomes are duplicated only during the
S phase
© 2014 Pearson Education, Inc.
Figure 9.6
G1
S
(DNA synthesis)
G2
© 2014 Pearson Education, Inc.
 Mitosis is conventionally divided into five phases
 Prophase
 Prometaphase
 Metaphase
 Anaphase
 Telophase
 Cytokinesis overlaps the latter stages of mitosis
© 2014 Pearson Education, Inc.
Video: Animal Mitosis
Video: Microtubules Mitosis
VIDEO: Mitosis
Video: Microtubules Anaphase
Video: Nuclear Envelope
10 m
Figure 9.7a
G2 of Interphase
Centrosomes
(with centriole
pairs)
Nucleolus
Chromosomes Early mitotic
Centromere
(duplicated,
spindle
Aster
uncondensed)
Nuclear
envelope
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Prophase
Plasma
membrane
Two sister chromatids of
one chromosome
Prometaphase
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
10 m
Figure 9.7b
Metaphase
Anaphase
Metaphase
plate
Spindle
Centrosome at
one spindle pole
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Telophase and
Cytokinesis
Cleavage
furrow
Daughter
chromosomes
Nuclear
envelope
forming
Nucleolus
forming
Figure 9.7c
G2 of Interphase
Centrosomes
(with centriole
pairs)
Chromosomes
(duplicated,
uncondensed)
Nucleolus Nuclear
envelope
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Plasma
membrane
Prophase
Early mitotic
Centromere
spindle
Aster
Two sister chromatids of
one chromosome
Figure 9.7d
Prometaphase
Fragments
of nuclear
envelope
Kinetochore
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Metaphase
Nonkinetochore
microtubules
Kinetochore
microtubule
Metaphase
plate
Spindle
Centrosome at
one spindle pole
Figure 9.7e
Telophase and
Cytokinesis
Anaphase
Cleavage
furrow
Daughter
chromosomes
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Nuclear
envelope
forming
Nucleolus
forming
10 m
Figure 9.7f
G2 of Interphase
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10 m
Figure 9.7g
Prophase
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10 m
Figure 9.7h
Prometaphase
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10 m
Figure 9.7i
Metaphase
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10 m
Figure 9.7j
Anaphase
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10 m
Figure 9.7k
Telophase and
Cytokinesis
© 2014 Pearson Education, Inc.
The Mitotic Spindle: A Closer Look
 The mitotic spindle is a structure made of
microtubules and associated proteins
 It controls chromosome movement during mitosis
 In animal cells, assembly of spindle microtubules
begins in the centrosome, the microtubule
organizing center
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 The centrosome replicates during interphase,
forming two centrosomes that migrate to opposite
ends of the cell during prophase and prometaphase
 An aster (radial array of short microtubules) extends
from each centrosome
 The spindle includes the centrosomes, the spindle
microtubules, and the asters
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 During prometaphase, some spindle microtubules
attach to the kinetochores of chromosomes and
begin to move the chromosomes
 Kinetochores are protein complexes that assemble
on sections of DNA at centromeres
 At metaphase, the centromeres of all the
chromosomes are at the metaphase plate, an
imaginary structure at the midway point between
the spindle’s two poles
© 2014 Pearson Education, Inc.
Video: Mitosis Spindle
Figure 9.8
Aster
Sister
chromatids
Centrosome
Metaphase plate
(imaginary)
Kinetochores
Microtubules
Chromosomes
Overlapping
nonkinetochore
microtubules Kinetochore
microtubules
1 m
0.5 m
© 2014 Pearson Education, Inc.
Centrosome
Figure 9.8a
Microtubules
Chromosomes
1 m
Centrosome
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Figure 9.8b
Kinetochores
Kinetochore
microtubules
0.5 m
© 2014 Pearson Education, Inc.
 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
 Chromosomes are also “reeled in” by motor proteins
at spindle poles, and microtubules depolymerize
after they pass by the motor proteins
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Figure 9.9
Experiment
Results
Kinetochore
Spindle
pole
Conclusion
Mark
Chromosome
movement
Motor
protein
Chromosome
Microtubule
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Kinetochore
Tubulin
subunits
Figure 9.9a
Experiment
Kinetochore
Spindle
pole
Mark
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Figure 9.9b
Results
Conclusion
Chromosome
movement
Motor
Microtubule
protein
Chromosome
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Kinetochore
Tubulin
subunits
 Nonkinetochore microtubules from opposite poles
overlap and push against each other, elongating
the cell
 At the end of anaphase, duplicate groups of
chromosomes have arrived at opposite ends of the
elongated parent cell
 Cytokinesis begins during anaphase or telophase
and the spindle eventually disassembles
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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
© 2014 Pearson Education, Inc.
© 2014 Pearson Education, Inc.
Animation: Cytokinesis
© 2014 Pearson Education, Inc.
Video: Cytokinesis and Myosin
Figure 9.10
(a) Cleavage of an animal cell (SEM)
Cleavage furrow
Contractile ring of
microfilaments
100 m
(b) Cell plate formation in a plant cell (TEM)
Vesicles
forming
cell plate
Wall of parent
1 m
cell
Cell plate New cell wall
Daughter cells
Daughter cells
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Figure 9.10a
(a) Cleavage of an animal cell (SEM)
Cleavage furrow
Contractile ring of
microfilaments
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100 m
Daughter cells
Figure 9.10aa
Cleavage furrow
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100 m
Figure 9.10b
(b) Cell plate formation in a plant cell (TEM)
Vesicles
forming
cell plate
Wall of parent
1 m
cell
Cell plate New cell wall
Daughter cells
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Figure 9.10ba
Vesicles
forming
cell plate
© 2014 Pearson Education, Inc.
Wall of parent
cell
1 m
Figure 9.11
Nucleus
Chromosomes
Nucleolus condensing
Chromosomes
10 m
1 Prophase
2 Prometaphase
Cell plate
3 Metaphase
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4 Anaphase
5 Telophase
Figure 9.11a
Chromosomes
Nucleus
Nucleolus condensing
10 m
1 Prophase
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Figure 9.11b
Chromosomes
10 m
2 Prometaphase
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Figure 9.11c
3 Metaphase
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10 m
Figure 9.11d
4 Anaphase
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10 m
Figure 9.11e
Cell plate
5 Telophase
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10 m
Binary Fission in Bacteria
 Prokaryotes (bacteria and archaea) reproduce by a
type of cell division called binary fission
 In E. coli, the single chromosome replicates,
beginning at the origin of replication
 The two daughter chromosomes actively move apart
while the cell elongates
 The plasma membrane pinches inward, dividing the
cell into two
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Figure 9.12-1
Origin of
replication
E. coli cell
1 Chromosome
replication
begins.
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Two copies
of origin
Cell wall
Plasma
membrane
Bacterial
chromosome
Figure 9.12-2
Origin of
replication
E. coli cell
1 Chromosome
replication
begins.
2 One copy of the
origin is now at
each end of the
cell.
© 2014 Pearson Education, Inc.
Two copies
of origin
Origin
Cell wall
Plasma
membrane
Bacterial
chromosome
Origin
Figure 9.12-3
Origin of
replication
E. coli cell
1 Chromosome
replication
begins.
2 One copy of the
origin is now at
each end of the
cell.
3 Replication
finishes.
© 2014 Pearson Education, Inc.
Two copies
of origin
Origin
Cell wall
Plasma
membrane
Bacterial
chromosome
Origin
Figure 9.12-4
Origin of
replication
E. coli cell
1 Chromosome
replication
begins.
2 One copy of the
origin is now at
each end of the
cell.
3 Replication
finishes.
4 Two daughter
cells result.
© 2014 Pearson Education, Inc.
Two copies
of origin
Origin
Cell wall
Plasma
membrane
Bacterial
chromosome
Origin
The Evolution of Mitosis
 Since prokaryotes evolved before eukaryotes,
mitosis probably evolved from binary fission
 Certain protists (dinoflagellates, diatoms, and some
yeasts) exhibit types of cell division that seem
intermediate between binary fission and mitosis
© 2014 Pearson Education, Inc.
Figure 9.13
Chromosomes
Microtubules
Intact nuclear
envelope
(a) Dinoflagellates
Kinetochore
microtubule
Intact nuclear
envelope
(b) Diatoms and some yeasts
© 2014 Pearson Education, Inc.
Concept 9.3: The eukaryotic cell cycle is
regulated by a molecular control system
 The frequency of cell division varies with the type
of cell
 These differences result from regulation at the
molecular level
 Cancer cells manage to escape the usual controls
on the cell cycle
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Evidence for Cytoplasmic Signals
 The cell cycle is driven by specific signaling
molecules present in the cytoplasm
 Some evidence for this hypothesis comes from
experiments with cultured mammalian cells
 Cells at different phases of the cell cycle were fused
to form a single cell with two nuclei at different
stages
 Cytoplasmic signals from one of the cells could
cause the nucleus from the second cell to enter the
“wrong” stage of the cell cycle
© 2014 Pearson Education, Inc.
Figure 9.14
Experiment
Experiment 1
S
G1
Experiment 2
M
G1
Results
S
S
G1 nucleus
immediately entered
S phase and DNA
was synthesized.
M
M
G1 nucleus began
mitosis without
chromosome
duplication.
Conclusion Molecules present in the cytoplasm
control the progression to S and M phases.
© 2014 Pearson Education, Inc.
Checkpoints of 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 timing device of a washing machine
 The cell cycle control system is regulated by both
internal and external controls
 The clock has specific checkpoints where the cell
cycle stops until a go-ahead signal is received
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Figure 9.15
G1 checkpoint
Control
system
G1
M
G2
M checkpoint
G2 checkpoint
© 2014 Pearson Education, Inc.
S
 For many cells, the G1 checkpoint seems to be the
most important
 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
© 2014 Pearson Education, Inc.
Figure 9.16
G1 checkpoint
G0
G1
G1
Without go-ahead signal,
cell enters G0.
(a) G1 checkpoint
S
M
G1
With go-ahead signal,
cell continues cell cycle.
G2
G1
G1
M G2
M
G2
M checkpoint
Prometaphase
Without full chromosome
attachment, stop signal is
received.
(b) M checkpoint
© 2014 Pearson Education, Inc.
Anaphase
G2
checkpoint
Metaphase
With full chromosome
attachment, go-ahead signal
is received.
Figure 9.16a
G1 checkpoint
G0
G1
Without go-ahead signal,
cell enters G0.
(a) G1 checkpoint
© 2014 Pearson Education, Inc.
G1
With go-ahead signal,
cell continues cell cycle.
Figure 9.16b
G1
G1
M G2
M
G2
M checkpoint
Prometaphase
Without full chromosome
attachment, stop signal is
received.
(b) M checkpoint
© 2014 Pearson Education, Inc.
Anaphase
G2
checkpoint
Metaphase
With full chromosome
attachment, go-ahead signal
is received.
 The cell cycle is regulated by a set of regulatory
proteins and protein complexes including kinases
and proteins called cyclins
© 2014 Pearson Education, Inc.
 An example of an internal signal occurs at the M
phase checkpoint
 In this case, anaphase does not begin if any
kinetochores remain unattached to spindle
microtubules
 Attachment of all of the kinetochores activates a
regulatory complex, which then activates the enzyme
separase
 Separase allows sister chromatids to separate,
triggering the onset of anaphase
© 2014 Pearson Education, Inc.
 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
© 2014 Pearson Education, Inc.
Figure 9.17-1
Scalpels
1 A sample of
human connective
tissue is cut
up into small
pieces.
Petri
dish
© 2014 Pearson Education, Inc.
Figure 9.17-2
Scalpels
1 A sample of
human connective
tissue is cut
up into small
pieces.
Petri
dish
2 Enzymes digest
the extracellular
matrix, resulting
in a suspension of
free fibroblasts.
© 2014 Pearson Education, Inc.
Figure 9.17-3
Scalpels
1 A sample of
human connective
tissue is cut
up into small
pieces.
Petri
dish
2 Enzymes digest
the extracellular
matrix, resulting
in a suspension of
free fibroblasts.
3 Cells are transferred
to culture vessels.
4 PDGF is added to
half the vessels.
© 2014 Pearson Education, Inc.
Figure 9.17-4
Scalpels
1 A sample of
human connective
tissue is cut
up into small
pieces.
Petri
dish
2 Enzymes digest
the extracellular
matrix, resulting
in a suspension of
free fibroblasts.
3 Cells are transferred
to culture vessels.
4 PDGF is added to
half the vessels.
Without PDGF
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With PDGF
Cultured fibroblasts
(SEM)
10 m
Figure 9.17a
Cultured fibroblasts
(SEM)
© 2014 Pearson Education, Inc.
10 m
 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
 Cancer cells exhibit neither density-dependent
inhibition nor anchorage dependence
© 2014 Pearson Education, Inc.
Figure 9.18
Anchorage dependence: cells
require a surface for division
Density-dependent inhibition:
cells form a single layer
Density-dependent inhibition:
cells divide to fill a gap and
then stop
20 m
(a) Normal mammalian cells
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20 m
(b) Cancer cells
Figure 9.18a
20 m
(a) Normal mammalian cells
© 2014 Pearson Education, Inc.
Figure 9.18b
20 m
(b) Cancer cells
© 2014 Pearson Education, Inc.
Loss of Cell Cycle Controls in Cancer Cells
 Cancer cells do not respond to signals that normally
regulate the cell cycle
 Cancer cells may not need growth factors to grow
and divide
 They may make their own growth factor
 They may convey a growth factor’s signal without the
presence of the growth factor
 They may have an abnormal cell cycle control system
© 2014 Pearson Education, Inc.
 A normal cell is converted to a cancerous cell by a
process called transformation
 Cancer cells that are not eliminated by the immune
system form tumors, masses of abnormal cells within
otherwise normal tissue
 If abnormal cells remain only 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 additional
tumors
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5 m
Figure 9.19
Breast cancer cell
(colorized SEM)
Lymph
vessel
Metastatic
tumor
Tumor
Blood
vessel
Cancer
cell
Glandular
tissue
1 A tumor grows
from a single
cancer cell.
© 2014 Pearson Education, Inc.
2 Cancer cells
invade
neighboring
tissue.
3 Cancer cells spread
through lymph and
blood vessels to
other parts of the
body.
4 A small percentage
of cancer cells may
metastasize to
another part of the
body.
Figure 9.19a
Tumor
Glandular
tissue
1 A tumor grows
from a single
cancer cell.
© 2014 Pearson Education, Inc.
2 Cancer cells
invade
neighboring
tissue.
3 Cancer cells spread
through lymph and
blood vessels to
other parts of the
body.
Figure 9.19b
Lymph
vessel
Metastatic
tumor
Blood
vessel
Cancer
cell
3 Cancer cells spread
through lymph and
blood vessels to
other parts of the
body.
© 2014 Pearson Education, Inc.
4 A small percentage
of cancer cells may
metastasize to
another part of the
body.
5 m
Figure 9.19c
Breast cancer cell
(colorized SEM)
© 2014 Pearson Education, Inc.
 Recent advances in understanding the cell cycle
and cell cycle signaling have led to advances in
cancer treatment
 Medical treatments for cancer are becoming more
“personalized” to an individual patient’s tumor
 One of the big lessons in cancer research is how
complex cancer is
© 2014 Pearson Education, Inc.
Figure 9.UN01
Control
200
A B C
Treated
A B C
Number of cells
160
120
80
40
0
0
200
400
600
0
200
400
600
Amount of fluorescence per cell (fluorescence units)
© 2014 Pearson Education, Inc.
Figure 9.UN02
G1
S
Cytokinesis
Mitosis
G2
MITOTIC (M) PHASE
Prophase
Telophase and
Cytokinesis
Prometaphase
Anaphase
Metaphase
© 2014 Pearson Education, Inc.
Figure 9.UN03
© 2014 Pearson Education, Inc.