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The Cell Cycle
Chapter 12A.P. Biology
• Overview: The Key Roles of Cell Division
• The continuity of life:
– is based upon the reproduction of cells, or
cell division
Figure 12.1
Unicellular organisms:
– Reproduce by cell division.
(a) Reproduction. An amoeba,
a single-celled eukaryote, is
dividing into two cells. Each
new cell will be an individual
organism (LM).
Figure 12.2 A
100 µm
• In binary fission:
– The bacterial chromosome replicates
– The two daughter chromosomes
actively move apart
1
Chromosome replication begins.
Soon thereafter, one copy of the
origin moves rapidly toward the
other end of the cell.
Origin of
replication
Cell wall
Plasma
Membrane
E. coli cell
Two copies
of origin
2
3
4
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.
Figure 12.11
Origin
Bacterial
Chromosome
Origin
Cell Replication in Bacteria
• Cell division in bacteria is controlled by
the size of the cell; volume of the
cytoplasm.
• Bacteria replicate by binary fission.
• >22 enzymes copy the DNA as a circle.
• Both copies of the DNA are attached to
the plasma membrane.
The Evolution of Mitosis
• Since prokaryotes preceded
eukaryotes by billions of years:
–It is likely that mitosis evolved from
bacterial cell division
• Certain protists:
–Exhibit types of cell division that
seem intermediate between binary
fission and mitosis carried out by
most eukaryotic cells
A hypothetical sequence for the evolution of
(a)
Prokaryotes. During binary fission, the origins of mitosis
the daughter
Bacterial
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.
chromosome
Chromosomes
(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
Microtubules
Intact nuclear
envelope
Kinetochore
microtubules
Intact nuclear
envelope
Kinetochore
microtubules
Centrosome
Fragments of
nuclear envelope
Multicellular organisms depend on cell
division for:
– Development from a fertilized cell
– Growth
– Repair
200 µm
(b) Growth and development.
This micrograph shows a
sand dollar embryo shortly
after the fertilized egg divided,
forming two cells (LM).
Figure 12.2 B, C
(c) Tissue renewal. These dividing
bone marrow cells (arrow) will
give rise to new blood cells (LM).
20 µm
Cell Division in Eukaryotic Cells
• Eukaryotic cells are much larger.
• Also have larger genomes (the sum of
an organisms’s genetic information).
• Eukaryotic DNA is organized into much
more complex structures.
• Why?
The DNA molecules in a cell
– Are packaged into chromosomes.
Figure 12.3
50 µm
Chromosomes of Eukaryotes
• Chromosomes are composed of
chromatin - a DNA/protein complex.
• Chromatin = 40% DNA + 60% Protein.
• Every 200 nucleotides , the DNA duplex
coils around a core of eight histone
proteins = Nucleosome.
Regions of Chromosomes are Not the Same
• Condensed portions of chromatin Heterochromatin - are not being
expressed; genes are turned off. May
never be turned on.
• Other portions of chromosome are
decondensed and are being actively
transcribed - Euchromatin. These
areas are only condensed during cell
division.
Karyotype
How Many Chromosomes are in Cells?
• Most body or somatic cells have two
copies of almost identical chromosomes
- diploid. Ex. Humans have 23 types of
chromosomes X 2 = 46 (2n or diploid
number).
• Sex cells or gametes (egg and sperm)
have only one copy of each
chromosome - haploid. Ex. Human
sperm/egg = 23 chromosomes.
Continued
• Some somatic cells are truly unusual.
• Human liver cells have 4 copies of all
chromosomes - tetraploid.
• Other cells RBC’s have no nucleus and
therefore, no chromosomes.
Phases of the Cell Cycle
• The cell cycle consists of
– The mitotic phase
– Interphase
INTERPHASE
G0
G1
S
(DNA synthesis)
G2
Figure 12.5
Chromosome Terminology
• The two copies of each chromosome in
somatic cells - homologous
chromosomes (homologues). Are
these the same?
• Before cell division, each homologue
replicates --> two sister chromatids
that are joined at the centromere.
• Each duplicated chromosome:
– Has two sister chromatids, which separate
during cell division
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
0.5 µm
Chromosome
duplication
(including DNA
synthesis)
Centromere
Separation
of sister
chromatids
Centromeres
Sister
chromatids
Sister chromatids
• Mitosis consists of five distinct phases
– Prophase
– Prometaphase
G2 OF INTERPHASE
Centrosomes
(with centriole pairs)
Figure 12.6
Nucleolus
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
– Metaphase
– Anaphase
– Telophase
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
The Mitotic Spindle: A Closer
Look
• The mitotic spindle:
– Is an apparatus of microtubules that controls
chromosome movement during mitosis.
• Some spindle microtubules:
– Attach to the kinetochores of
chromosomes and move the chromosomes
Centrosome
to the metaphase Aster
plate
Sister
chromatids
Metaphase
Plate
Kinetochores
Overlapping
nonkinetochore
microtubules
Kinetochores microtubules
Microtubules
Figure 12.7
0.5 µm
Chromosomes
Centrosome
1 µm
• In anaphase, sister chromatids separate:
– And move along the kinetochore microtubules
toward opposite ends of the cell
EXPERIMENT
1 The microtubules of a cell in early anaphase were labeled with a fluorescent dye
that glows in the microscope (yellow).
Kinetochore
Spindle
pole
Figure 12.8
• Nonkinetechore 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
Animal Cells have Centrioles
Cell Cycle
G0
Enter Mitosis!
Interphase
Prophase
Prophase and Microtubules
Metaphase
Anaphase
Telophase
•
Cytokinesis: A Closer
Look
In animal cells
– Cytokinesis occurs by a process known as
cleavage, forming a cleavage furrow
Cleavage furrow
100 µm
Contractile ring of
microfilaments
Figure 12.9 A
Daughter cells
(a) Cleavage of an animal cell (SEM)
• In plant cells, during cytokinesis:
– A cell plate forms.
Vesicles
forming
cell plate
Wall of
patent cell
1 µm
Cell plate
New cell wall
Daughter cells
Figure 12.9 B
(b) Cell plate formation in a plant cell (SEM)
Plant vs. Animal Mitosis
•
•
•
•
Plant Cells
Lack centrioles
No aster
Assemble
membrane
components in the
interior- cell plate
Deposts cellulosenew cell wall.
Animal Cells
• Use centrioles
• Centrioles
develop an
aster
• Actin filaments
constrict the cell
-cleavage
furrow.
What’s the overall goal of mitosis?
What happens when cells
divide out of control?
Cell Cycle Control
• Internal clocks are not flexible.
• Eukaryotic cells use Check Pointsenzymes that survey conditions of
the cell and act as “go/no go”
switches.
• Regulated by feedback from the
cell.
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
G1 checkpoint
Control
system
G1
M
G2
M checkpoint
Figure 12.14
G2 checkpoint
S
• The clock has specific checkpoints:
– Where the 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 go-ahead
signal at the G1checkpoint, the cell
exits the cell cycle and goes into G0, a
nondividing state.
Three Principal Checkpoints
• G1 Checkpoint (also called START)end of G1/beginning of S- decision to
replicate DNA.
• Surveys cell size and environmental
conditions.
G1 Checkpoint
Replicate
DNA
Cell Size?
Favorable
Conditions?
Yes
No
Grow or G
G2 Checkpoint
• Occurs at the end of G2 and triggers
mitosis.
G2 Checkpoint
DNA
Replicated?
Cell Size?
Growth
Conditions?
Mitosis
Yes
No
Pause
M Check Point
• Occurs at metaphase, triggers exit
from mitosis and beginning of G1.
M Check Point
Are
Anaphase
All
Yes
Chromosomes
Aligned?
No
Pause
Checkpoints Regulated by Enzymes
• Cyclins- proteins that appear and
disappear at different points in the cell
cycle.
• Cyclin-Dependent Kinases(Cdk’s)- enzymes that phosphorylate
other enzymes and proteins. Not
active w/o cyclins.
The activity of cyclins and Cdks
fluctuates during the cell cycle
(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 G , conditions in
1
the cell favor degradation
of cyclin, and the Cdk
component of MPF is
recycled.
Cdk
Degraded
Cyclin
Cyclin is
degraded
4 During anaphase, the cyclin component
Figure 12.16 A, B
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.
Regulating the Cell Cycle
Example: Figure 11.23
• At the G2 checkpoint, use
Cdk + cyclin -----> MPF
(Mitosis Promoting
Factor)
Evidence for Cytoplasmic Signals
• Molecules present in the cytoplasm
– Regulate progress through the cell cycle
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.
Controlling the Cell Cycle
• Growth Factors. Over 50 so far, many
work at G1 checkpoint; bind to surface
receptors of cells. Ex. PDGF.
• Contact Inhibition. Normal cells stop
growing when they make contact with
other cells; use surface receptors.
• Growth factors:
– Stimulate other cells to divide
EXPERIMENT
Scalpels
1 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
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.
Figure 12.17
With PDGF
Without PDGF
• In density-dependent inhibition (contact inhibition):
– Crowded cells stop dividing
• Most animal cells exhibit anchorage dependence
– In which they must be attached to a substratum to divide
(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
– Exhibit 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
• Malignant tumors invade surrounding tissues
and can metastasize
– Exporting cancer cells to other parts of the body
where they may form secondary tumors
Tumor
Lymph
vessel
Blood
vessel
Glandular
tissue
Cancer cell
1 A tumor grows from a
single cancer cell.
Figure 12.19
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.
Controlling the Cell Cycle-17.6 lb tumor!
How do Growth Factors Work?
• G. F.’s allow passage through G1
checkpoint by causing more cyclins to
be formed.
• Some genes normally stimulate cell
division- protooncogenes.
Two Types of Cell Division Control
• Positive Controls- like growth factors,
stimulate cell division.
• Negative Controls- like tumor
suppressors, prevent cell division. Ex.
p53.
p53 Tumor Suppressor
Delays cycle at G1
until DNA repaired.
Is DNA p53
Damaged?
If irrepairable,causes
apoptosis(programmed
cell death).
If p53 is not functioning,
leads to mutations->cancer.
Controlling Cell Growth
• The case of retinoblastoma.
• Some genes normally inhibit cell
division- tumor suppressor genes.
• Example: In GO, Rb protein is
dephosphorylated and binds to the
Myc protein, preventing its promoting
of cell division.
A Fun Review of the Cell Cycle