Chapter 9
Chapter 9
Sylvia S. Mader
Michael Windelspecht
Chapter 9
The Cell Cycle and
Cellular
Reproduction
Lecture Outline
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1
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Outline
• 9.1 The Cell Cycle
• 9.2 Mitosis and Cytokinesis
• 9.3 The Cell Cycle and Cancer
• 9.4 Prokaryotic Cell Division
2
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)
Mitotic Stage (includes mitosis and cytokinesis)
3
The Cell Cycle
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Interphase
S
G1 checkpoint
(growth and DNA
Cell cycle main checkpoint. G1 replication) G2 checkpoint
If DNA is damaged, apoptosis G2
will occur. Otherwise, the cell G1 Mitosis checkpoint.
(growth and final Mitosis will occur
is committed to divide when G0 (growth) preparations for G
growth signals are present M 2 if DNA has
s division)
si replicated properly.
e
and nutrients are available.
ase
ne
as
se
e
se
i as Apoptosis will
h
ok
ha
h
op
Anapha
t
Metaph
op occur if the DNA is
Cy
op
pr
Pr
damaged and
te
Tel
La
cannot be repaired.
M
M checkpoint
Spindle assembly
checkpoint. Mitosis
will not continue if
chromosomes are
not properly aligned.
4
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 G0 stage)
5
The Cell Cycle
• Interphase consists of: G1, S, and G2 phases
G1 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
G2 Phase:
• Between DNA replication and onset of mitosis
• Cell synthesizes proteins necessary for division
6
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
cells
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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 G1, M or G2
(checkpoints)
• Allows time for any damage to be repaired
8
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 decreases cell number
9
Apoptosis
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apoptotic cell
blebs
DNA
fragment
10
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 G1 when DNA is
damaged
• Initiates an attempt at DNA repair
– If successful, the cycle continues to
mitosis
– If not, apoptosis is initiated
11
Regulation at the G1
Checkpoint
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a.
no DNA
damage breakdown
of p53
p53 p53 binds to DNA.
DNA
damage P P P
P DNA DNA
phosphorylated p53
DNA repair apoptosis
proteins
b.
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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
chromosome number
13
Diploid Chromosome Numbers of
Some Eukaryotes
14
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
– One set of 23 from individual’s father (paternal)
– Other set of 23 from individual’s mother (maternal)
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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
daughter nuclei
16
Duplicated Chromosomes
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sister chromatids
centromere
kinetochore
one chromatid
a. 9,850 b.
© Andrew Syred/Photo Researchers, Inc.
17
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
• Centrosome was also replicated in S-phase, so
there are two centrosomes before mitosis begins
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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
• Microtubules form star-like arrays termed asters
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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)
» These connect sister chromatids to opposite poles of
the mother cell
20
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
– Pulled to opposite poles along kinetochore fibers
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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
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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
opposite sides of the middle lamella
24
Cytokinesis in Animal Cells
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X 4,000
Cleavage furrow
Contractile ring
X 4,000
25
(top): © Thomas Deerinck/Visuals Unlimited; (bottom): © SPL/Getty RF
Cytokinesis in Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
daughter cells
vesicles containing
nucleoli membrane components
fusing to form cell plate
daughter
nucleus
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Phases of Mitosis in Animal and
Plant Cells
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centrosome
has centrioles
nuclear
centromere
envelope kinetochore
fragments nucleolus
MITOSIS
chromatin
condenses
nucleolus kinetochore
disappears spindle spindle fiber kinetochore
fibers forming spindle fiber
polar spindle fiber Metaphase Telophase
Early Prophase Prophase Prophase Centromeres of duplicated chromosomes Anaphase Daughter cells are forming
Centrosomes have duplicated. Nucleolus has disappeared, and Nucleolus has disappeared, and are aligned at the metaphase plate (center Sister chromatids part and become daughter
Chromatin is condensing into duplicated chromosomes are visible. duplicated chromosomes are visible. of fully formed spindle). Kinetochore spindle chromosomes that move toward the spindle
as nuclear envelopes and
chromosomes, and the nuclear Centrosomes begin moving apart, Centrosomes begin moving apart, fibers attached to the sister chromatids poles. In this way, each pole receives the same nucleoli reappear. Chromosomes will
centrosome envelope is fragmenting. and spindle is in process of forming. and spindle is in process of forming. come from opposite spindle poles. number and kinds of chromosomes as the parent cell. become indistinct chromatin.
lacks centrioles
Plant Cell
at Interphase spindle pole lacks
25µm 6.2µm 20µm 6.2µm
cell wall chromosomes centrioles and aster spindle fibers 6.2µm cell plate 6.6µm
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;
27
Phases of Mitosis in Animal and Plant Cells
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centrosome
has centrioles
Animal Cell
at Interphase 20 µm
aster
nuclear
envelope
fragments Early Prophase
Centrosomes have duplicated.
MITOSIS
chromatin
condenses Chromatin is condensing into
nucleolus
disappears
chromosomes, and the nuclear
Early Prophase envelope is fragmenting.
centrosome
lacks centrioles
Plant Cell
at Interphase
25 µm
centrosome
has centrioles
Animal Cell
at Interphase 20 µm duplicated 20 µm
aster
chromosome
nuclear
envelope Prophase
centromere
fragments
Nucleolus has disappeared, and
MITOSIS
chromatin
duplicated chromosomes are
condenses
nucleolus visible. Centrosomes begin moving
disappears
spindle
fibers forming apart, and spindle is in process
Early Prophase
Centrosomes have duplicated.
Prophase
of forming.
Chromatin is condensing into
chromosomes, and the nuclear
envelope is fragmenting.
centrosome
lacks centrioles
Plant Cell
at Interphase
25 µm 6.2 µm
cell wall chromosomes
Animal cell(Early prophase, Prophase): © Ed Reschke; Plant cell(Early prophase): © Ed Reschke; Plant cell(Prophase): © R. Calentine/Visuals Unlimited
Phases of Mitosis in Animal and Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
centrosome
has centrioles
Animal Cell
at Interphase 20 µm duplicated 20 µm spindle 9 µm
aster
chromosome pole
nuclear kinetochore
envelope centromere
Prometaphase
fragments
The kinetochore of each
MITOSIS
chromatin
chromatid is attached to a
condenses
nucleolus kinetochore spindle fiber. Polar
disappears kinetochore
spindle spindle fiber
fibers forming
polar spindle fiber
spindle fibers stretch from each
Prometaphase
Early Prophase
Centrosomes have duplicated.
Prophase
Nucleolus has disappeared, and
spindle pole and overlap.
Chromatin is condensing into duplicated chromosomes are visible.
chromosomes, and the nuclear Centrosomes begin moving apart,
envelope is fragmenting. and spindle is in process of forming.
centrosome
lacks centrioles
Plant Cell
at Interphase 25 µm 6.2 µm 20 µm
cell wall chromosomes spindle pole lacks
centrioles and aster
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
Phases of Mitosis in Animal and Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
centrosome
has centrioles
Metaphase
Animal Cell
at Interphase aster
20 µm duplicated
chromosome
20 µm spindle
pole
9 µm chromosomes at
metaphase plate
20 µm Centromeres of duplicated
nuclear kinetochore
envelope centromere chromosomes are aligned at the
fragments
chromatin
condenses
formed spindle). Kinetochore
kinetochore
nucleolus
disappears
spindle
kinetochore
spindle fiber
spindle fiber
spindle fibers attached to the
fibers forming
polar spindle fiber
Early Prophase Prophase Prometaphase Metaphase
sister chromatids come from
Centrosomes have duplicated. Nucleolus has disappeared, and The kinetochore of each chromatid is
Chromatin is condensing into
chromosomes, and the nuclear
duplicated chromosomes are visible.
Centrosomes begin moving apart,
attached to a kinetochore spindle fiber.
Polar spindle fibers stretch from each
opposite spindle poles.
envelope is fragmenting. and spindle is in process of forming. spindle pole and overlap.
centrosome
lacks centrioles
Plant Cell
at Interphase
25 µm 6.2 µm spindle pole lacks 20 µm 6.2 µm
cell wall chromosomes spindle fibers
centrioles and aster
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
Phases of Mitosis in Animal and Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
centrosome
has centrioles
Animal Cell
at Interphase 20 µm duplicated 20 µm spindle 9 µm chromosomes at 20 µm 20 µm
Anaphase
aster daughter chromosome
chromosome pole metaphase plate
nuclear kinetochore Sister chromatids part and become
envelope
centromere
fragments
daughter chromosomes that move
toward the spindle poles. In this
MITOSIS
chromatin
condenses
nucleolus
way, each pole receives the same
disappears kinetochore
spindle
fibers forming
spindle fiber kinetochore number and kinds of chromosomes
spindle fiber
polar spindle fiber
Early Prophase Prophase Prometaphase Metaphase
Centromeres of duplicated chromosomes
Anaphase as the parent cell.
Centrosomes have duplicated. Nucleolus has disappeared, and The kinetochore of each chromatid is
Chromatin is condensing into duplicated chromosomes are visible. attached to a kinetochore spindle fiber. are aligned at the metaphase plate (center
chromosomes, and the nuclear Centrosomes begin moving apart, Polar spindle fibers stretch from each of fully formed spindle). Kinetochore spindle
envelope is fragmenting. and spindle is in process of forming. spindle pole and overlap. fibers attached to the sister chromatids
come from opposite spindle poles.
centrosome
lacks centrioles
Plant Cell
at Interphase
25 µm 6.2 µm spindle pole lacks 20 µm 6.2 µm 6.2 µm
cell wall chromosomes spindle fibers
centrioles and aster
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
Phases of Mitosis in Animal and Plant Cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
centrosome
has centrioles
Animal Cell
20 µm duplicated 20 µm spindle 9 µm chromosomes at 20 µm 20 µm 16 µm
at Interphase aster daughter chromosome cleavage furrow
chromosome pole metaphase plate
nuclear
envelope
kinetochore Telophase
centromere nucleolus
fragments
Daughter cells are forming
MITOSIS
Plant Cell
at Interphase 25 µm 6.2 µm 20 µm 6.2 µm 6.2 µm 6.6 µm
cell wall chromosomes spindle pole lacks spindle fibers cell plate
centrioles and aster
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;
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
• A cut heals or a broken bone mends
34
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
cloning, the production of a new individual
35
Reproductive and Therapeutic
Cloning
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remove and
discard egg
egg nucleus
remove Implant
fuse egg embryo
Go nucleus
with Go into
Go cells from nucleus culture surrogate
animal to be mother
cloned embryonic
stem cells Clone is born
a. Reproductive cloning remove and
discard egg
egg nucleus
nervous
remove
fuse egg
Go nucleus
with Go blood
Go somatic cells nucleus culture
embryonic
stem cells muscle
b. Therapeutic cloning
36
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
May take years before a cell is obviously cancerous
37
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
• Cancer cells are abnormal but fail to undergo apoptosis
38
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
– Brings nutrients and oxygen to the tumor
39
Progression of Cancer
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New mutations arise, and one cell (brown) has the ability to start a tumor.
primary tumor
lymphatic blood
vessel vessel
Cancer in situ. The tumor is at its place of origin. One cell (purple)
mutates further.
lymphatic blood
vessel vessel
Cancer cells now have the ability to invade lymphatic and blood vessels
and travel throughout the body.
New metastatic tumors are found some distance from the primary tumor.
40
Cancer Cells vs. Normal Cells
41
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
genes are normally regulated in coordination
with organism’s growth plan
42
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:
• Cause telomeres to continue to lengthen, which
• Allows cancer cells to continually divide
43
Causes of
Cancer
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Heredity Radiation
sources
growth
factor
growth factor Viruses
receptor Activates signaling Pesticides
protein proteins in a stimulatory and oncogene
pathway that extends herbicides
to the nucleus.
P
a. Influences that cause mutated proto-oncogenes
P
(called oncogenes) and mutated tumor
suppressor genes
activated
P signaling
protein
signaling
Stimulatory
protein
pathway gene product
phosphate
promotes
b. Effect of growth factor cell cycle
proto-oncogene
Codes for a growth factor,
a receptor protein, or a
signaling protein in a
stimulatory pathway.
If a proto-oncogene
becomes an oncogene,
the end result can be
active cell division.
44
9.4 Prokaryotic Cell Division
• The prokaryotic chromosome is a ring of DNA
Folded up in an area called the nucleoid
1,000 X the length of cell
Replicated into two rings prior to cell division
Replicated rings attach to the plasma membrane
• Binary fission
Splitting in two
Two replicate chromosomes are distributed to two
daughter cells
Produces two daughter cells identical to original cell –
asexual reproduction
45
Binary Fission
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chromosome
1. Attachment of chromosome to cell wall
a special plasma membrane
site indicates that this plasma
bacterium is about to divide. membrane
cytoplasm
chromosome
1. Attachment of chromosome to cell wall
a special plasma membrane
site indicates that this plasma
bacterium is about to divide. membrane
cytoplasm
chromosome
1. Attachment of chromosome to cell wall
a special plasma membrane
site indicates that this plasma
bacterium is about to divide. membrane
cytoplasm
chromosome
1. Attachment of chromosome to cell wall
a special plasma membrane
site indicates that this plasma
bacterium is about to divide. membrane
cytoplasm
chromosome
1. Attachment of chromosome to cell wall
a special plasma membrane
site indicates that this plasma
bacterium is about to divide. membrane
cytoplasm
51