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Ch. 12 – The Cell Cycle
• The ability of organisms to reproduce best
distinguishes living things from nonliving matter
• The continuity of life is based on the
reproduction of cells, or cell division
•
Cell division is an
integral part of the
cell cycle, the life
of a cell from
formation to its own
division
• In unicellular organisms, division of one cell
reproduces the entire organism
100 µm
(a) Reproduction
20 µm
200 µm
(b) Growth and
development
(c) Tissue renewal
• Multicellular organisms depend on cell division
for: (1) Development from a fertilized cell, (2)
Growth, and (3) Repair
12.1: Cell division results in genetically
identical daughter cells
• Most cell division results in daughter cells with
identical genetic information, DNA
• A special type of division produces nonidentical
daughter cells (gametes, or sperm and egg
cells)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Every eukaryotic species has a characteristic
number of chromosomes in each cell nucleus
• Eukaryotic chromosomes consist of
chromatin, a complex of DNA and protein that
condenses during cell division
• Somatic cells (nonreproductive cells) have
two sets of chromosomes
– They are considered diploid (2n)
• Gametes (reproductive cells: sperm and eggs)
have half as many chromosomes as somatic
cells
– They are considered haploid (n)
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,
which separate during cell
division
• The centromere is the narrow
“waist” of the duplicated
chromosome, where the two
chromatids are most closely
attached
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-4
0.5 µm
Chromosomes
Chromosome arm
DNA molecules
Chromosome
duplication
(including DNA
synthesis)
Centromere
Sister
chromatids
Separation of
sister chromatids
Centromere
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 © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Walther Flemming
Samples of Walther Flemming’s drawings
Copyright © 2008 Pearson Education, Inc., publishing as Pearson 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”)
• The cell grows during all
three phases, but
chromosomes are
duplicated only during the
S phase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Mitosis is
conventionally
divided into five
phases:
– Prophase
– Prometaphase
– Metaphase
– Anaphase
– Telophase
• Cytokinesis is well
underway by late
telophase
BioFlix: Mitosis
G
G22 of
of Interphase
Interphase
Chromatin
Centrosomes
(with centriole (duplicated)
pairs)
Prophase
Prophase
Early mitotic Aster
spindle
Nucleolus Nuclear Plasma
envelope membrane
Centromere
Chromosome, consisting
of two sister chromatids
Prometaphase
Prometaphase
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
Metaphase
Metaphase
Anaphase
Anaphase
Metaphase
plate
Spindle
Centrosome at
one spindle pole
Telophase
Cytokinesis
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
• During prophase, assembly of spindle
microtubules begins in the centrosome, the
microtubule organizing center (video – 1:14)
• The centrosome replicates, forming two
centrosomes that migrate to opposite ends of
the cell, as spindle microtubules grow out from
them
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• An aster (a radial array of short microtubules)
extends from each centrosome
• The spindle includes the centrosomes, the
spindle microtubules, and the asters
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• During prometaphase, some spindle
microtubules attach to the kinetochores of
chromosomes and begin to move the
chromosomes
• At metaphase, the chromosomes are all lined
up at the metaphase plate, the midway point
between the spindle’s two poles (video – 0:19)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-7
Aster
Centrosome
Sister
chromatids
Microtubules
Chromosomes
Metaphase
plate
Kinetochores
Centrosome
1 µm
Overlapping
nonkinetochore
microtubules
Kinetochore
microtubules
0.5 µm
• In anaphase, sister
chromatids separate &
move along the
kinetochore microtubules
toward opposite ends of
the cell (video – 0:23)
• The microtubules shorten
by depolymerizing at their
kinetochore ends
EXPERIMENT
Kinetochore
Spindle
pole
Mark
RESULTS
CONCLUSION
Chromosome
movement
Kinetochore
Motor
Microtubule protein
Chromosome
Tubulin
subunits
• 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 (video –
0:40)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson 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 © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Video: Animal Mitosis
Video: Sea Urchin (Time Lapse)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
100 µm
Cleavage furrow
Contractile ring of
microfilaments
Vesicles
forming
cell plate
Wall of
parent cell
Cell plate
1 µm
New cell wall
Daughter cells
(a) Cleavage of an animal cell (SEM)
Daughter cells
(b) Cell plate formation in a plant cell (TEM)
Fig. 12-10
• Review of the Cell Cycle (animation)
Nucleus
Nucleolus
1 Prophase
Chromatin
condensing
Chromosomes
2 Prometaphase
3 Metaphase
Cell plate
4 Anaphase
5 Telophase
10 µm
Binary Fission
• Prokaryotes (bacteria
and archaea)
reproduce by a type of
cell division called
binary fission
(animation)
• In binary fission, the
chromosome replicates
(beginning at the
origin of replication),
and the two daughter
chromosomes actively
move apart
Cell wall
Origin of
replication
E. coli cell
Two copies
of origin
Origin
Plasma
membrane
Bacterial
chromosome
Origin
The Evolution of Mitosis
• Since prokaryotes
evolved before
eukaryotes, mitosis
probably evolved from
binary fission
Bacterial
chromosome
(a) Bacteria
Chromosomes
Microtubules
Intact nuclear
envelope
(b) Dinoflagellates
• Certain protists exhibit
types of cell division
that seem intermediate
between binary fission
and mitosis
Kinetochore
microtubule
Intact nuclear
envelope
(c) Diatoms and yeasts
Kinetochore
microtubule
• Animation – comparing
bacteria/plants/animals
Fragments of
nuclear envelope
(d) Most eukaryotes
12.3: The eukaryotic 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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 © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-13
EXPERIMENT
Experiment 1
S
G1
Experiment 2
M
G1
RESULTS
S
S
When a cell in the
S phase was fused
with a cell in G1, the G1
nucleus immediately
entered the S
phase—DNA was
synthesized.
M
M
When a cell in the
M phase was fused with
a cell in G1, the G1
nucleus 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 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 (animation)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-14
G1 checkpoint
Control
system
G1
M
G2
M checkpoint
G2 checkpoint
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 © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-15
G0
G1 checkpoint
G1
(a) Cell receives a go-ahead
signal
G1
(b) Cell does not receive a
go-ahead signal
The Cell Cycle Clock: Cyclins and
Cyclin-Dependent Kinases
• Two types of regulatory proteins are involved in
cell cycle control: cyclins and cyclindependent kinases (Cdks)
• The activity of cyclins and Cdks fluctuates
during the cell cycle
• MPF (maturation-promoting factor) is a cyclinCdk complex that triggers a cell’s passage past
the G2 checkpoint into the M phase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-16
RESULTS
5
30
4
20
3
2
10
1
0
100
200
300
Time (min)
400
0
500
Fig. 12-17
M
S
G1
G2
M
G1
S
G2
M
G1
MPF activity
Cyclin
concentration
Time
(a) Fluctuation of MPF activity and cyclin concentration during
the cell cycle
Degraded
cyclin
G2
checkpoint
Cyclin is
degraded
MPF
Cdk
Cyclin
(b) Molecular mechanisms that help regulate the cell cycle
Cyclin accumulation
Cdk
Recap -- Role of Cyclin-dependent kinases
• Rhythmic fluctuations of control molecules pace the
cell cycle.
– Some molecules are protein kinases that activate or
deactivate other proteins by phosphorylating them.
• These kinases are present at constant levels, but
they are only activated in the presence of a second
protein - cyclin.
– The complex of kinases and cyclin forms cyclindependent kinases (Cdks).
– CDKs can be compared to an engine and cyclins to a
gear box controlling whether the engine will idle or
drive the cell forward into the next stage.
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Some external signals are growth factors,
proteins released by certain cells that stimulate
other cells to divide (animation)
• For example, plateletderived growth factor
(PDGF) stimulates the
division of human
fibroblast cells in culture
Scalpels
Petri
plate
Without PDGF
cells fail to divide
With PDGF
cells proliferate
Cultured fibroblasts
10 µm
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Cancer cells exhibit neither density-dependent
inhibition nor anchorage dependence
Anchorage dependence
Density-dependent inhibition
Density-dependent inhibition
25 µm
25 µm
(a) Normal mammalian cells
(b) Cancer cells
Loss of Cell Cycle Controls in Cancer Cells
•Video clip
• Cancer cells do not respond normally to the
body’s control mechanisms
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• A normal cell is converted to a cancerous cell
by a process called transformation
• 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 -- Video clip (NOVA)
•Video clip (CancerQuest)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-20
Lymph
vessel
Tumor
Blood
vessel
Cancer
cell
Metastatic
tumor
Glandular
tissue
1 A tumor grows
from a single
cancer cell.
2 Cancer cells
invade neighboring tissue.
3 Cancer cells spread
to other parts of
the body.
4 Cancer cells may
survive and
establish a new
tumor in another
part of the body.
Genetic Basis of Cancer
• Mutations altering genes for growth factors,
receptors, or signaling molecules can lead to
cancer.
• Video clip
Oncogenes and Proto-oncogenes
• Oncogenes =
cancer-causing
genes
• Video clip – Genes
II: Oncogenes
• Proto-oncogenes =
“normal” versions of
these genes; code
for proteins that
stimulate normal cell
growth / division
Mutations are one way that protooncogenes can become oncogenes.
• When a proto-oncogene becomes an
oncogene, there is an excess of the normal
growth-stimulating proteins
• Cells also contain genes whose products normally prevent
uncontrolled cell growth
– These are called tumor-suppressor genes (video clip
– Genes III: Tumor Suppressors)
– A mutation that decreases tumor-suppressor gene
activity may contribute to the onset of cancer
ras gene = a Proto-oncogene
• Mutations in this gene occur in 30% of
human cancers
• This gene encodes a G protein that relays a
signal that ultimately stimulates the cell cycle
– Normally, the pathway only begins when
triggered by a growth factor
– Mutations can send the Ras protein into
overdrive, causing it to relay the signal – and
bring about increased cell division – when
there is no growth factor
p53 – a Tumor-Suppressor Gene
• Mutations in this gene occur in over 50% of
human cancers
• A normal p53 gene encodes a protein that
prevents a cell from completing the cell cycle
if the cell’s DNA is damaged
Minor damage  cell cycle
halts until damage is
repaired
Major damage  cell will
undergo apoptosis
(programmed cell death)
Development of Cancer
• More than
one mutation
is generally
needed to
produce all
of the
changes
characteristic
of a cancer
cell.
This is one of the reasons why cancer is more common as we get
older (more time for more mutations to accumulate).
Inherited Predisposition to Cancer
• Certain cancers run in some families
– A person who inherits an oncogene or a
mutated tumor-suppressor gene is one step
closer to accumulating the mutations
necessary to develop cancer
• About 15% of colorectal cancers involve
inherited mutations
– Most affect a tumor-suppressor gene - APC
(adenomatous polyposis coli) – that
regulates cell migration and adhesion
• 5-10% of patients
with breast cancer
have an inherited
predisposition
– Most have
mutations in
either the
BRAC1 or
BRAC2 genes
– These are
tumor
suppressor
genes.
• Inside Cancer
Comprehensive Review of cancer