Biology
Sylvia S. Mader
Michael Windelspecht
Chapter 9
The Cell Cycle and
Cellular
Reproduction
Lecture Outline
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Outline
• 9.1 The Cell Cycle
• 9.2 Mitosis and Cytokinesis
9.1 The Cell Cycle
• The
cell cycle
is an orderly set of stages
from the first division to the time the
resulting daughter cells divide
• Just prior to the next division:
The cell grows larger
The number of organelles doubles
The DNA is replicated
• The two major stages of the cell cycle:
Interphase
(includes several stages)
The Cell Cycle
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G
1
(growth)
G
0
G
2
checkpoint
Mitosis checkpoint.
Mitosis will occur
if DNA has
replicated properly.
Apoptosis will
occur if the DNA is
damaged and
cannot be repaired.
S
(growth and DNA
replication)
M
Interphase
G1 checkpoint
Cell cycle main checkpoint.
If DNA is damaged, apoptosis
will occur. Otherwise, the cell
is committed to divide when
growth signals are present
and nutrients are available.
M checkpoint
Spindle assembly
checkpoint. Mitosis
will not continue if
chromosomes are
not properly aligned.
M
G
2
G
1
G
2
(growth and final
preparations for
The Cell Cycle
• Interphase
Most of the cell cycle is spent in
interphase
Cell performs its usual functions
Time spent in interphase varies by cell
type
Nerve and muscle cells do not
complete the cell cycle (remain in the
The Cell Cycle
• Interphase consists of: G
1
, S, and G
2
phases
G
1
Phase:
• Recovery from previous division
• Cell doubles its organelles
• Cell grows in size
• Cell accumulates raw materials for DNA synthesis
S Phase:
• DNA replication
• Proteins associated with DNA are synthesized
• Chromosomes enter with 1
chromatid
each
• Chromosomes leave with 2 identical chromatids (
sister
chromatids
) each
G
2
Phase:
The Cell Cycle
• M (Mitotic) Stage
Includes:
•
Mitosis
– Nuclear division
– Daughter chromosomes are distributed by the
mitotic
spindle
to two daughter nuclei
•
Cytokinesis
– Division of the cytoplasm
Results in two genetically identical daughter
The Cell Cycle
• The cell cycle is controlled by internal and
external signals
• A
signal
is a molecule that either stimulates or
inhibits a metabolic event.
Internal signals
• Family of proteins called
cyclins
that increase and
decrease as the cell cycle continues
• Without cyclins, the cell cycle stops at G
1
, M or G
2
(checkpoints)
The Cell Cycle
•
Apoptosis
is programmed cell death
• It involves a sequence of cellular events:
fragmenting of the nucleus,
blistering of the plasma membrane
engulfing of cell fragments
.
• Apoptosis is caused by enzymes called
caspases.
• Mitosis and apoptosis are opposing forces
Mitosis increases cell number
Apoptosis
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apoptotic cell
cell
fragment
DNA
fragment
Cell rounds
up, and nucleus
collapses.
Chromatin
condenses, and
nucleus fragments.
Plasma membrane
blisters, and blebs
form.
Cell fragments
contain DNA
fragments.
blebs
The Cell Cycle
• Apoptosis
Cells harbor caspases that are kept in
check by inhibitors
• Can be unleashed by internal or external
signals
Signal protein
p53
• Stops the cell cycle at G
1
when DNA is
damaged
• Initiates an attempt at DNA repair
–If successful, the cycle continues to
mitosis
Regulation at the G1
Checkpoint
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a.
P
P
RB
protein
RB
protein
E2F
E2F
E2F
CDK
not present
E2F not released
released
E2F
E2F binds to DNA.
DNA
cell cycle
proteins
phosphorylated RB
CDK present
P
P
P
P
breakdown
of p53
no DNA
damage
DNA
damage
phosphorylated p53
DNA repair
proteins
apoptosis
p53 binds to DNA.
9.2 Mitosis and Cytokinesis
• DNA is in very long threads
Chromosomes
Stretched out and intertwined between divisions
DNA is associated with
histones
(proteins)
DNA and histone proteins are collectively called
chromatin
• Before mitosis begins:
Chromatin condenses (coils) into distinctly
visible chromosomes
Each species has a characteristic
Mitosis and Cytokinesis
• The
diploid
(2n)
number includes two sets
of chromosomes of each type
Humans have 23 different types of
chromosomes
• Each type is represented twice in each body cell
(diploid)
• Only sperm and eggs have one of each type
·termed
haploid (n)
The haploid (n) number for humans is 23
• Two representatives of each chromosome type
• Makes a total of 2n = 46 in each nucleus
Mitosis and Cytokinesis
• At the end of S phase:
Each chromosome internally duplicated
Consists of two identical DNA chains
• Sister chromatids (two strands of genetically identical
chromosomes)
• Attached together at a single point (called
centromere
)
• During mitosis:
Centromeres holding sister chromatids together
separate
Sister chromatids separate
Each becomes a daughter chromosome
Sisters of each type are distributed to opposite
Duplicated Chromosomes
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centromere
sister chromatids
one chromatid
a.
b.
kinetochore
Mitosis and Cytokinesis
• Just outside the nucleus is the
centrosome
This is the microtubule organizing center in animal
cells
Organizes the mitotic spindle
• Contains many fibers
• Each fiber is composed of a bundle of microtubules
In animals, the centrosome contains two
barrel-shaped
centrioles
• Oriented at right angles to each other within the centrosome
• Each has 9 triplets of microtubules arranged in a cylinder
Mitosis and Cytokinesis
• Phases of Mitosis:
Prophase
• Chromatin has condensed
– Chromosomes are distinguishable with microscope
– Each chromosome has two sister chromatids attached at
the centromere
• Nucleolus disappears
• Nuclear envelope disintegrates
• Spindle begins to assemble
• The two centrosomes move away from each other
Mitosis and Cytokinesis
• Phases of Mitosis
Prometaphase
• The centromere of each chromosome
develops two kinetochores
– Specialized protein complex
– One attached to each sister chromatid
» Physically connect sister chromatids with specialized
microtubules (
kinetochores
)
Mitosis and Cytokinesis
• Stages of Mitosis
Metaphase
• Chromosomes are pulled around by kinetochore fibers
• Forced to align across the equatorial plane of the cell
–
Metaphase plate -
Represents plane through which
mother cell will be divided
Anaphase
• Centromere dissolves, releasing sister chromatids
• Sister chromatids separate
– Now called daughter chromosomes
Mitosis and Cytokinesis
• Stages of Mitosis
Telophase
• Spindle disappears
• Now two clusters of daughter chromosomes
– Still two of each type with all types represented
– Clusters are incipient daughter nuclei
• Nuclear envelopes form around the two
incipient daughter nuclei
Mitosis and Cytokinesis
• Cytokinesis = division of cytoplasm
• Allocates the mother cell’s cytoplasm equally to
daughter nucleus
• Encloses each daughter cell in its own plasma
membrane
• Often begins in anaphase
• Animal cytokinesis:
A
cleavage furrow
appears between daughter nuclei
Formed by a contractile ring of actin filaments
Like pulling on a drawstring
Mitosis and Cytokinesis
• Cytokinesis in plant cells begins with the formation of a
cell plate
Rigid cell walls outside plasma membrane do not
permit furrowing
Many small membrane-bounded vesicles
Eventually fuse into one thin vesicle extending across
the mother cell
The membranes of the cell plate become the plasma
membrane between the daughter cells
The space between the daughter cells becomes filled
with the middle lamella
Daughter cells later secrete primary cell walls on
Cytokinesis in Animal Cells
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Cleavage furrow
Contractile ring
Cytokinesis in Plant Cells
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daughter cells
nucleoli
daughter
nucleus
cell plate formation
daughter nucleus
vesicles containing
membrane components
fusing to form cell plate
Phases of Mitosis in Animal and
Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Animal cell(Early prophase, Prophase, Metaphase, Anaphase, Telophase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.;
Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase, Anaphase): © R. Calentine/Visuals Unli mited; Plant cell(Telophase): © Jack M.
Bostrack/Visuals Unlimited;
Plant Cell at Interphase centromere aster kinetochorepolar spindle fiber
chromosomes cell wall 25µm centrosome lacks centrioles M IT O SI S centrosome has centrioles Animal Cell at Interphase nuclear envelope fragments chromatin condenses nucleolus disappears Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting.
Prophase Nucleolus has disappeared, and duplicated chromosomes are visible.
Centrosomes begin moving apart, and spindle is in process of forming.
Prophase Nucleolus has disappeared, and duplicated chromosomes are visible.
Centrosomes begin moving apart, and spindle is in process of forming. 20 µm duplicated
chromosome 20 µm
spindle fibers forming
spindle pole 9 µm
kinetochore spindle fiber
cleavage furrow
spindle fibers
20µm 16µm
kinetochore spindle fiber
Anaphase Sister chromatids part and become daughter chromosomes that move toward the spindle poles. In this way, each pole receives the same number and kinds of chromosomes as the parent cell. Metaphase
Centromeres of duplicated chromosomes are aligned at the metaphase plate (center of fully formed spindle). Kinetochore spindle
fibers attached to the sister chromatids come from opposite spindle poles.
chromosomes at metaphase plate
6.2µm 6.2µm
20µm 6.2µm spindle pole lacks centrioles and aster
Telophase
Daughter cells are forming
as nuclear envelopes and
nucleoli reappear. Chromosomes will
become indistinct chromatin.
daughter chromosome 20µm nucleolus
Phases of Mitosis in Animal and Plant Cells
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Early Prophase
aster
20 µm
25 µm
MIT
OSI
S
Early Prophase
Centrosomes have duplicated.
Chromatin is condensing into
chromosomes, and the nuclear
envelope is fragmenting.
chromatin
condenses
nucleolus
disappears
nuclear
envelope
fragments
Animal Cell
at Interphase
centrosome
has centrioles
centrosome
lacks centrioles
Phases of Mitosis in Animal and Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Animal cell(Early prophase, Prophase): © Ed Reschke; Plant cell(Early prophase): © Ed Reschke; Plant cell(Prophase): © R. Cal entine/Visuals Unlimited
Prophase
spindle
fibers forming
centromere
aster
chromosomes
cell wall
20 µm
20 µm
6.2 µm
25 µm
Prophase
Nucleolus has disappeared, and
duplicated chromosomes are
visible. Centrosomes begin moving
apart, and spindle is in process
of forming.
MI
T
OSI
S
centrosome
lacks centrioles
Animal Cell
at Interphase
centrosome
has centrioles
nuclear
envelope
fragments
chromatin
condenses
nucleolus
disappears
Early Prophase
Centrosomes have duplicated.
Chromatin is condensing into
chromosomes, and the nuclear
envelope is fragmenting.
duplicated
chromosome
Phases of Mitosis in Animal and Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Animal cell(Early prophase, Prophase, Metaphase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.;
Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase): © R. Calentine/Visuals Unlimited
Prometaphase
centromere
spindle
pole
aster
kinetochore
polar spindle fiber
chromosomes
cell wall
20 µm
20 µm
6.2 µm
25 µm
20 µm
9 µm
Prometaphase
The kinetochore of each
chromatid is attached to a
kinetochore spindle fiber. Polar
spindle fibers stretch from each
spindle pole and overlap.
centrosome
has centrioles
Animal Cell
at Interphase
nuclear
envelope
fragments
chromatin
condenses
nucleolus
disappears
spindle
fibers forming
Early Prophase
Centrosomes have duplicated.
Chromatin is condensing into
chromosomes, and the nuclear
envelope is fragmenting.
Prophase
Nucleolus has disappeared, and
duplicated chromosomes are visible.
Centrosomes begin moving apart,
and spindle is in process of forming.
kinetochore
spindle fiber
duplicated
chromosome
Phases of Mitosis in Animal and Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Animal cell(Early prophase, Prophase, Metaphase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.;
Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase): © R. Calentine/Visuals Unlimited
duplicated
chromosome
centromere
aster
kinetochore
polar spindle fiber
chromosomes
cell wall
20 µm
6.2 µm
25 µm
20 µm
9 µm
spindle fibers
20 µm
6.2 µm
Metaphase
Centromeres of duplicated
chromosomes are aligned at the
metaphase plate (center of fully
formed spindle). Kinetochore
spindle fibers attached to the
sister chromatids come from
opposite spindle poles.
centrosome
has centrioles
Animal Cell
at Interphase
nuclear
envelope
fragments
nucleolus
disappears
chromatin
condenses
centrosome
lacks centrioles
Early Prophase
Centrosomes have duplicated.
Chromatin is condensing into
chromosomes, and the nuclear
envelope is fragmenting.
Prophase
Nucleolus has disappeared, and
duplicated chromosomes are visible.
Centrosomes begin moving apart,
and spindle is in process of forming.
Prometaphase
The kinetochore of each chromatid is
attached to a kinetochore spindle fiber.
Polar spindle fibers stretch from each
spindle pole and overlap.
Metaphase
kinetochore
spindle fiber
chromosomes at
metaphase plate
spindle
pole
kinetochore
spindle fiber
spindle
fibers forming
Plant Cell
at Interphase
spindle pole lacks
centrioles and aster
Phases of Mitosis in Animal and Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Animal cell(Early prophase, Prophase, Metaphase, Anaphase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.;
Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase, Anaphase): © R. Calentine/Visuals Unlimited
centromere spindle pole aster kinetochore kinetochore spindle fiber polar spindle fiber
chromosomes cell wall
20 µm 20 µm
6.2 µm
25 µm 20 µm
9 µm daughter chromosome
spindle fibers
20 µm 20 µm
6.2 µm 6.2 µm centrosome has centrioles Animal Cell at Interphase nuclear envelope fragments nucleolus disappears chromatin condenses centrosome lacks centrioles Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting.
Prophase Nucleolus has disappeared, and duplicated chromosomes are visible.
Centrosomes begin moving apart, and spindle is in process of forming.
Prometaphase The kinetochore of each chromatid is attached to a kinetochore spindle fiber.
Polar spindle fibers stretch from each spindle pole and overlap.
Metaphase Centromeres of duplicated chromosomes are aligned at the metaphase plate (center of fully formed spindle). Kinetochore spindle
fibers attached to the sister chromatids come from opposite spindle poles.
kinetochore spindle fiber
Anaphase chromosomes at
metaphase plate
spindle pole lacks centrioles and aster Plant Cell at Interphase duplicated chromosome spindle fibers forming
M
IT
OS
IS
Anaphase
Phases of Mitosis in Animal and Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
centromere aster
kinetochore
polar spindle fiber
chromosomes cell wall
20 µm 20 µm
6.2 µm
25 µm 20 µm
9 µm daughter chromosome
spindle fibers cell plate
20 µm 20 µm 16 µm
6.2 µm 6.6 µm 6.2 µm
nucleolus
cleavage furrow
Telophase
Daughter cells are forming
as nuclear envelopes and
nucleoli reappear.
Chromosomes will
become indistinct chromatin.
centrosome has centrioles Animal Cell at Interphase nuclear envelope fragments chromatin condenses nucleolus disappears centrosome lacks centrioles Plant Cell at Interphase Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting.
spindle fibers forming
duplicated chromosome
kinetochore spindle fiber Prophase
Nucleolus has disappeared, and duplicated chromosomes are visible.
Centrosomes begin moving apart, and spindle is in process of forming.
Prometaphase The kinetochore of each chromatid is attached to a kinetochore spindle fiber.
Polar spindle fibers stretch from each spindle pole and overlap.
Metaphase Centromeres of duplicated chromosomes are aligned at the metaphase plate (center of fully formed spindle). Kinetochore spindle
fibers attached to the sister chromatids come from opposite spindle poles.
Anaphase Sister chromatids part and become daughter chromosomes that move toward the spindle poles. In this way, each pole receives the same number and kinds of chromosomes as the parent cell.
Telophase
spindle pole lacks centrioles and aster
spindle pole
chromosomes at metaphase plate
kinetochore spindle fiber
Animal cell(Early prophase, Prophase, Metaphase, Anaphase, Telophase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.; Plant cell(Early prophase, Prometaphse):
© Ed Reschke; Plant cell(Prophase, Metaphase, Anaphase): © R. Calentine/Visuals Unlimited; Plant cell(Telophase): © Jack M. Bostrack/Visuals Unlimited;
M
IT
O
S
Phases of Mitosis in Animal
and Plant Cells
•
Functions of mitosis:
Permits growth and repair.
In flowering plants, meristematic tissue
retains the ability to divide throughout the
life of the plant
In mammals, mitosis is necessary when:
•
A fertilized egg becomes an embryo
•
An embryo becomes a fetus
Phases of Mitosis in Animal
and Plant Cells
•
Stem Cells
Many mammalian organs contain stem cells
•
Retain the ability to divide
•
Red bone marrow stem cells divide to produce various
types of blood cells
Therapeutic cloning
to produce human tissues
can begin with either adult stem cells or embryonic
stem cells
Embryonic stem cells can be used for
reproductive
Reproductive and Therapeutic
Cloning
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remove and
discard egg
nucleus
egg
remove
G
o
nucleus
G
o
cells from
animal to be
cloned
egg
fuse egg
with G
o
nucleus
Implant
embryo
into
surrogate
mother
Clone is born
culture
embryonic
stem cells
nervous
blood
muscle
embryonic
stem cells
culture
fuse egg
with G
o
nucleus
remove and
discard egg
nucleus
G
o
somatic cells
remove
G
o
nucleus
9.3 The Cell Cycle and Cancer
• Abnormal growth of cells is called a
tumor
Benign
tumors are not cancerous
• Encapsulated
• Do not invade neighboring tissue or spread
Malignant
tumors are cancerous
• Not encapsulated
• Readily invade neighboring tissues
• May also detach and lodge in distant places (metastasis)
• Results from mutation of genes regulating the cell cycle
• Development of
cancer
Tends to be gradual
The Cell Cycle and Cancer
• Characteristics of Cancer Cells
Lack differentiation
• Are non-specialized
• Are immortal (can enter cell cycle repeatedly)
Have abnormal nuclei
• May be enlarged
• May have abnormal number of chromosomes
• Often have extra copies of genes
Do not undergo apoptosis
• Normally, cells with damaged DNA undergo apoptosis
• The immune system can also recognize abnormal cells and
trigger apoptosis
The Cell Cycle and Cancer
• Characteristics of Cancer Cells
Form tumors
• Mitosis is normally controlled by contact with
neighboring cells – contact inhibition
• Cancer cells have lost contact inhibition
Undergo metastasis
• Original tumor easily fragments
• New tumors appear in other organs
Undergo
angiogenesis
• Formation of new blood vessels
Progression of Cancer
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primary tumor
New mutations arise, and one cell (brown) has the ability to start a tumor.
Cancer in situ. The tumor is at its place of origin. One cell (purple)
mutates further.
Cancer cells now have the ability to invade lymphatic and blood vessels
and travel throughout the body.
lymphatic
vessel
blood
vessel
lymphatic
vessel
The Cell Cycle and Cancer
• Origin of Cancer
Oncogenes
•
Proto-oncogenes
promote the cell cycle in
various ways
• If a proto-oncogene is mutated, it may become an
oncogene
Tumor suppressor genes
inhibit the cell
cycle in various ways
• If a tumor suppressor gene becomes inactive, it
may promote cancer development
Both proto-oncogenes and tumor suppressor
The Cell Cycle and Cancer
• Origin of Cancer
Chromosomes normally have special material
at each end called
telomeres
These get shorter each cell division
When they get very short, the cell will no
longer divide
Telomerase is an enzyme that maintains the
length of telomeres
Mutations in telomerase gene:
Causes of
Cancer
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activated signaling protein growth factor receptor protein signaling protein phosphate
b. Effect of growth factor
P
P P