Bellringer
Based on what you know about cell
signaling, write one paragraph explaining
why a medication that treats insulin
resistance in diabetic patients might cause
suicidal thoughts.
Chapter 12
The Cell Cycle
The Cell Cycle
The continuity of life is based on the ability
of a cell to reproduce, or divide.
Figure 12.1
Unicellular Organisms

Reproduce through cell division
◦ Mitosis
◦ Binary Fission
100 µm
(a) Reproduction. An amoeba,
a single-celled eukaryote, is
dividing into two cells. Each
new cell will be an individual
Figure 12.2 A
organism (LM).
Multicellular Organisms

Need cell division for:
◦ Development from a fertilized cell
◦ Growth
◦ Repair
200 µm
20 µm
(b) Growth and development.
(c) Tissue renewal. These dividing
This micrograph shows a
bone marrow cells (arrow) will
sand dollar embryo shortly
give rise to new blood cells (LM).
after the fertilized egg divided,
Figure 12.2 B, C forming two cells (LM).
Cell division
Results in genetically identical daughter
cells
 DNA replicated before cell division
 Genome – All of a cell’s genetic
information (DNA)

DNA Molecules

Packaged into
chromosomes
◦ Single molecules of
DNA
◦ Loosely organized
during most of
interphase
◦ Tightly packed
during cell division
Figure 12.3
50 µm
Eukaryotic Cells

Chromosomes made of chromatin
◦ complex of DNA & protein that condenses
during cell division

In animals
◦ Somatic cells have 2 sets of chromosomes
◦ Gametes have 1 set of chromosomes
Before cell division, chromosomes
replicate and condense

Two sister
chromatids
0.5 µm
A eukaryotic cell has multiple
chromosomes, one of which is
represented here. Before
duplication, each chromosome
has a single DNA molecule.
Once duplicated, a chromosome
consists of two sister chromatids
connected at the centromere. Each
chromatid contains a copy of the
DNA molecule.
Mechanical processes separate
the sister chromatids into two
chromosomes and distribute
them to two daughter cells.
Figure 12.4
Chromosome
duplication
(including DNA
synthesis)
Centromere
Separation
of sister
chromatids
Centromeres
Sister
chromatids
Sister chromatids
Eukaryotic Cells

Somatic cell division
◦ Mitosis- division of nucleus
◦ Cytokinesis- division of cytoplasm

Meiosis
◦ Sex cells (gametes) are produced after a
reduction in chromosome number (down to a
single set)
The Cell Cycle

Mitotic phase alternates with interphase in
the cell cycle
INTERPHASE
G1
S
(DNA synthesis)
G2
Figure 12.5
Phases of the Cell Cycle

Mitotic phase
INTERPHASE
◦ Mitosis
◦ Cytokinesis

G1
Interphase
◦ G1 phase (First gap)
◦ S phase (synthesis)
◦ G2 phase (second gap)
Figure 12.5
S
(DNA synthesis)
G2
Mitosis has five phases
G2 OF INTERPHASE
Centrosomes
(with centriole pairs)
Nucleolus
Figure 12.6
Nuclear
envelope
Chromatin
(duplicated)
Plasma
membrane
PROPHASE
Early mitotic
spindle
Aster
Centromere
Chromosome, consisting
of two sister chromatids
PROMETAPHASE
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
Mitosis has five phases
METAPHASE
ANAPHASE
Metaphase
plate
Figure 12.6
Spindle
Centrosome at
one spindle pole
TELOPHASE AND CYTOKINESIS
Cleavage
furrow
Daughter
chromosomes
Nuclear
envelope
forming
Nucleolus
forming
Prophase
Nuclear envelope starts to break down
 Chromosomes condense
 Centrosomes separate

Prometaphase
Nuclear envelope finishes breaking down
 Chromosomes completely condensed
 Microtubules attach to kinetochores
 Microtubules start to move chromosomes

Metaphase

Chromosomes line up on metaphase plate
Anaphase
Proteins holding sister chromatids
together become inactive
 Sister chromatids are pulled along spindle
fibers to opposite ends of the cell

Telophase
Nuclear envelope reforms on either side of
the cell
 Cytokinesis begins

Cytokinesis
Cytoplasm divides
 Cleavage furrow appears (animal cells)
 Cell plate forms (plant cells)

The Mitotic Spindle
Apparatus of microtubules that controls
chromosome movement during mitosis
 Spindle arises from the centrosomes

◦ Includes spindle microtubules & asters
The Mitotic Spindle

Spindle
microtubules
◦ Attach to the
kinetochores of
chromosomes &
move the
chromosomes to
the metaphase
plate
◦ Overlap and help to
elongate the cell by
pushing against
each other
Aster
Sister
chromatids
Centrosome
Metaphase
Plate
Kinetochores
Overlapping
nonkinetochore
microtubules
Kinetochores
microtubules
Microtubules
0.5 µm
Figure 12.7 Centrosome
1 µm
Chromosomes
Cytokinesis

Animal cells
◦ Cytokinesis occurs by
a process known as
cleavage, forming a
cleavage furrow
Cleavage furrow
Contractile ring of
microfilaments
Figure 12.9 A
100 µm
Daughter cells
(a) Cleavage of an animal cell (SEM)
Cytokinesis

In plant cells
◦ cell plate forms
out of vesicles
◦ Cell wall forms
after cell plate
Vesicles
forming
cell plate
1 µm
Wall of
patent cell Cell plate New cell wall
Daughter cells
Figure 12.9 B (b) Cell plate formation in a plant cell (SEM)
Mitosis in a plant cell
Chromatine
Nucleus
Nucleolus condensing
Chromosome
Metaphase. The
2 Prometaphase.
3
1 Prophase.
spindle is complete, 4
The chromatin
We now see discrete
and the chromosomes,
is condensing.
chromosomes; each
attached to microtubules
The nucleolus is
consists of two
at their kinetochores,
beginning to
identical sister
are all at the metaphase
disappear.
chromatids. Later
plate.
Although not
in prometaphase, the
yet visible
nuclear envelop will
in the micrograph,
fragment.
the mitotic spindle is
staring to from.
Figure 12.10
Anaphase. The
5
chromatids of each
chromosome have
separated, and the
daughter chromosomes
are moving to the ends
of cell as their
kinetochore
microtubles shorten.
Telophase. Daughter
nuclei are forming.
Meanwhile, cytokinesis
has started: The cell
plate, which will
divided the cytoplasm
in two, is growing
toward the perimeter
of the parent cell.
Binary Fission
Reproduction of prokaryotes
 Bacterial chromosome replicates
 Origin cite of replication on each
chromosome moves to opposite ends of
cell
 Cell divides

Binary Fission
Origin of
replication
Cell wall
E. coli cell
1 Chromosome replication begins.
Soon thereafter, one copy of the
origin moves rapidly toward the
other end of the cell.
2 Replication continues. One copy of
the origin is now at each end of
the cell.
3 Replication finishes. The plasma
membrane grows inward, and
new cell wall is deposited.
Figure 12.11 4 Two daughter cells result.
Two copies
of origin
Origin
Plasma
Membrane
Bacterial
Chromosome
Origin
The Evolution of Mitosis
Mitosis probably evolved from bacterial
cell division
 Certain protists

◦ Exhibit types of cell division that seem
intermediate between binary fission and
mitosis

A hypothetical sequence for the evolution of mitosis
(a) Prokaryotes. During binary fission, the origins of the
daughter chromosomes move to opposite ends of the
cell. The mechanism is not fully understood, but
proteins may anchor the daughter chromosomes to
specific sites on the plasma membrane.
(b) Dinoflagellates. In unicellular protists called
dinoflagellates, the nuclear envelope remains intact
during cell division, and the chromosomes attach to the
nuclear envelope. Microtubules pass through the
nucleus inside cytoplasmic tunnels, reinforcing the
spatial orientation of the nucleus, which then divides in a
fission process reminiscent of bacterial division.
(c) Diatoms. In another group of unicellular protists, the
diatoms, the nuclear envelope also remains intact
during cell division. But in these organisms, the
microtubules form a spindle within the nucleus.
Microtubules separate the chromosomes, and the
nucleus splits into two daughter nuclei.
(d) Most eukaryotes. In most other eukaryotes,
including plants and animals, the spindle forms
outside the nucleus, and the nuclear envelope
breaks down during mitosis. Microtubules separate
the chromosomes, and the nuclear envelope then
re-forms.
Figure 12.12 A-D
Bacterial
chromosome
Chromosomes
Microtubules
Intact nuclear
envelope
Kinetochore
microtubules
Intact nuclear
envelope
Kinetochore
microtubules
Centrosome
Fragments of
nuclear envelope
Cell Cycle Regulation
Cell cycle is regulated by a molecular
control system
 Frequency of cell division

◦ Varies depending on the type of cell

Cell cycle differences
◦ Result from regulation at the molecular level
◦ Regulatory molecules present in cytoplasm
Evidence for Cytoplasmic Signals
EXPERIMENTS In each experiment, cultured mammalian cells at two different phases of the cell cycle were induced to fuse.
Experiment 1
Experiment 2
S
G1
M
S
M
G1
RESULTS
S
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.
M
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.
CONCLUSION The results of fusing cells at two different phases of the cell cycle suggest that molecules present in the
Figure 12.13 A, B
cytoplasm of cells in the S or M phase control the progression of phases.
The Cell Cycle Control System

The sequential events of the cell cycle
◦ Directed by a distinct cell cycle control system,
which is similar to a clock
G1 checkpoint
Control
system
G1
M
M checkpoint
Figure 12.14
G2
G2 checkpoint
S
The Cell Cycle Control System

The clock has
specific
checkpoints
◦ Cell cycle stops
until a go-ahead
signal is received
G0
G1 checkpoint
G1
Figure 12.15 A, B
(a) If a cell receives a go-ahead
signal at
the G1 checkpoint, the cell
continues
on in the cell cycle.
G1
(b) If a cell does not receive a goahead
signal at the G1checkpoint, the cell
exits the cell cycle and goes into
G0, a
nondividing state.
The Cell Cycle Clock
Two types of regulatory proteins are
involved in cell cycle control
 Cyclins
 Cyclin-dependent kinases (Cdks)
 Activity of proteins fluctuate together

(a) Fluctuation of MPF activity and
cyclin concentration during
the cell cycle
M
G1 S G2 M
G1 S G2 M
MPF activity
Cyclin
Time
(b) Molecular mechanisms that
help regulate the cell cycle
1 Synthesis of cyclin begins in late S
phase and continues through G2.
Because cyclin is protected from
degradation during this stage, it
accumulates.
5 During G1, conditions in
the cell favor degradation
of cyclin, and the Cdk
component of MPF is
recycled.
gure 12.16 A, B
Cdk
Degraded
Cyclin
Cyclin is
degraded
4 During anaphase, the cyclin component
of MPF is degraded, terminating the M
phase. The cell enters the G1 phase.
G2
Cdk
checkpoint
MPF
Cyclin
2 Accumulated cyclin molecules
combine with recycled Cdk molecules, producing enough molecules of
MPF to pass the G2 checkpoint and
initiate the events of mitosis.
3 MPF promotes mitosis by phosphorylating
various proteins. MPF‘s activity peaks during
metaphase.
Internal and External Signals at
the Checkpoints

Stop and go signs
◦
◦
◦
◦
Control the cell cycle checkpoints
Example: Growth factors
Example: Density-dependent inhibition
Example: Anchorage dependence- must be
attached to a substratum to divide
EXPERIMENT
1
Scalpels
A sample of connective tissue was cut up
into small pieces.
Petri
plate
2 Enzymes were used to digest the extracellular matrix,
resulting in a suspension of free fibroblast cells.
3
Figure 12.17
Cells were transferred to sterile culture vessels
containing a basic growth medium consisting of
glucose, amino acids, salts, and antibiotics (as a
precaution against bacterial growth). PDGF was added
to half the vessels. The culture vessels were incubated
at 37°C.
With PDGF
Without PDGF
(a)
Normal mammalian cells. The
availability of nutrients, growth
factors, and a substratum for
attachment limits cell
density to a single layer.
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).
Figure 12.18 A
25 µm

Cancer cells
◦ show neither density-dependent inhibition nor
anchorage dependence
Cancer cells do not exhibit
anchorage dependence or
density-dependent inhibition.
(b) Cancer cells. Cancer cells usually
continue to divide well beyond a
single layer, forming a clump of
overlapping cells.
Figure 12.18 B
25 µm
Loss of Cell Cycle Controls in
Cancer Cells

Cancer cells
◦ Don’t respond normally to the body’s control
mechanisms
◦ Form tumors

Malignant tumors invade surrounding
tissues and can metastasize
◦ Exporting cancer cells to other parts of the
body where they may form secondary tumors
Lymph
vessel
Tumor
Blood
vessel
Glandular
tissue
1 A tumor grows from a
single cancer cell.
Figure 12.19
Cancer cell
2 Cancer cells invade
neighboring tissue.
3 Cancer cells spread
through lymph and
blood vessels to
other parts of the body.
Metastatic
Tumor
4 A small percentage of
cancer cells may survive
and establish a new tumor
in another part of the body.