Chapter 12: Cell Cycle
Chromosome Sorting
• The goal of cell division typically is to equally
partition two more-or-less identical copies of
genetic material between two daughter cells
• Prokaryotes are comparatively simple, with only
one chromosome, so have a relatively easy time
sorting daughter chromosomes to daughter cells
• Eukaryotes, with their longer DNA and multiple
chromosomes, don’t have it nearly so easy
• Much of the complex “dance” of Mitosis is a
consequence of the need to make sure that
each daughter cell ends up with the same
number and type of chromosomes as the
parent
Cell Division
• Important roles of cellular
division:
– Reproduction: Forms
duplicate offspring (amoeba).
– Growth and Development:
Allows single cell to form into
multicelluar organism
– Tissue Renewal: Cells are
damaged and die all the time.
These cells need to be
replaced.
Prokaryotic Reproduction Through
Mitosis
Chromosomal Differences
Prokaryote Chromosome
Eukaryote Chromosome
Here “chromosome”
and “DNA” are not
100% synonymous
Chromosomes vs. Chromatin
• Chromosomes
• Chromatin
• Tightly packaged DNA
• Found only during cell
division
• DNA is not being used for
macromolecule synthesis
• Unwound DNA
• Found throughout
Interphase
• DNA is being used for
macromolecule synthesis
Eukaryotic Chromosomes
Though chromosomes are
“all about” DNA, in fact much
this structure consists of
protein
Formed via
replication, not by
formed chromatids
coming together
How Long is a Chromatid??
• A chromatid is a chromatid as
long as it is held in association
with a sister chromatid at the
centromere
• When two sister
chromatids separate (after
metaphase) they go from
being a single
chromosome to being two
different chromosomes
Sister Chromatids
Chromatid
Chromosome
Eukaryotic Chromosome
Genome
= DNA
Chromosomes =
DNA + PROTEIN
(visible under light
microscope)
Chromatin =
DNA + PROTEIN
(unwound)
DNA
Important Vocabulary
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Centromere
Centrosome
Centriole
Kinetochore
Kinetochore microtubules
Mitotic spindle
Nonkinetochore microtubules
Spindle apparatus
Spindle fibers
Important Vocabulary
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2 Centrioles =
Centrosome
Centromere
Centrosome
Centriole
Kinetochore
Kinetochore microtubules
Mitotic spindle
Nonkinetochore microtubules
Spindle apparatus
Spindle fibers
Nonmembranous
organelles that
organize
microtubules
throughout the cell
cycle
Important Vocabulary
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Centromere
Centrosome
Centriole
Kinetochore
Kinetochore microtubules
Mitotic spindle
Nonkinetochore microtubules
Spindle apparatus
Spindle fibers
Comprised of
microtubules. Only
in animal cells! Not
necessary for
spindle formation.
Important Vocabulary
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Centromere
Centrosome
Centriole
Kinetochore
Kinetochore microtubules
Mitotic spindle
Nonkinetochore microtubules
Spindle apparatus
Spindle fibers
Attachment point on
Chromatids for spindle
fiber
Important Vocabulary
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Centromere
Centrosome
Centriole
Kinetochore
Kinetochore microtubules
Mitotic spindle
Nonkinetochore microtubules
Spindle apparatus
Spindle fibers
The portion of the
mitotic spindle that is
connected to the
chromosome during
mitosis
Important Vocabulary
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Centromere
Centrosome
Centriole
Kinetochore
Kinetochore microtubules
Mitotic spindle
Nonkinetochore microtubules
Spindle apparatus
Spindle fibers
The microtubules that
are responsible for
separating as well as
pushing centrosomes
towards the opposite
ends of the cells.
Important Vocabulary
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Centromere
Centrosome
Centriole
Kinetochore
Kinetochore microtubules
Mitotic spindle
Nonkinetochore microtubules
Spindle apparatus
Spindle fibers
Microtubules of the
mitotic spindle that
are not connected to
chromosomes but are
responsible for
pushing centrosomes
apart.
Important Vocabulary
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Centromere
Centrosome
Centriole
Kinetochore
Kinetochore microtubules
Mitotic spindle
Nonkinetochore microtubules
Spindle apparatus
Spindle fibers
The mitotic spindle as
visible through a light
microscope.
Important Vocabulary
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Centromere
Centrosome
Centriole
Kinetochore
Kinetochore microtubules
Mitotic spindle
Nonkinetochore microtubules
Spindle apparatus
Spindle fibers
Bundles of
microtubules that
comprise the spindle
apparatus. This
bundling is what
allows us to visualize
the fibers through a
light microscope
Phases of the Cell Cycle
(Eukaryotes)
• Interphase (not
mitosis)
• Mitosis
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Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis
Phases of the Cell Cycle
(Eukaryotes)
• Interphase
• Mitosis is the shortest
part of the cell cycle.
• Interphase accounts
for about 90% of the
cell cycle.
• Cells:
– Grow
– Copy chromosomes
– Prepare for cell
division
Phases of the Cell Cycle
(Eukaryotes)
• Interphase is divided
into subphases:
– G1 Phase = Gap 1
– S Phase = synthesis
– G2 Phase = Gap 2
• During all three
subphases, the cell
grows by producing
proteins and
organelles.
Figure 12.5 The stages of mitotic cell division: interphase
Late interphase
 Nucleus is well defined and
bounded by the nuclear envelope
 Duplicated chromosomes are
loosely packed chromatin fibers
 Microtubules extend from the
duplicated centrosomes
Figure 12.5 The stages of mitotic cell division: prophase
Prophase: 1st Phase of Mitosis
 Nucleoli disappear
 Chromatin fibers become tightly
coiled in the nucleus condensing
into discrete chromosomes
 Centrosomes move away from
each other as mitotic spindle begins
to form in the cytoplasm
Figure 12.5 The stages of mitotic cell division: prometaphase
Prometaphase
 Nuclear envelope fragments
 Chromosomes condense
further and form kinetochores
(structures at the centromere
region that microtubules bind)
 Microtubules extend from each
pole and invade the nuclear area
and either attach to kinetochores
or microtubules from the
opposite side
Figure 12.5 The stages of mitotic cell division : metaphase
Metaphase
 Centrisome are at opposite poles
 Chromosomes line up at the center
of the cell equidistant from each pole
(metaphase plate)
 Microtubules are attached to the
kinetochores of each sister chromatid
facing its pole
Figure 12.5 The stages of mitotic cell division : anaphase
Anaphase
 Paired centromeres of each
chromosome separate, dividing the
sister chromatids
 Centrosome poles move farther
apart
 Microtubules begin to shorten,
pulling their attached chromosome
towards opposite poles
Figure 12.5 The stages of mitotic cell division : telophase and
cytokinesis
Telophase
 Daughter nuclei form at the two poles
 Nuclear envelopes begin to form from
the fragments of the parent cell
 Chromatin fibers loosen
Cytokinesis
 A cleavage furrow forms between
daughter cells and the cell is pinched in
two, equally dividing the cytoplasm
Figure 12.5x Mitosis
Prometaphase
The Mitotic Spindle: A Closer
Look
• The mitotic spindle
– Is an apparatus of
microtubules that
controls chromosome
movement during mitosis
• The spindle arises from
the centrosomes
– And includes spindle
microtubules and asters
• Some spindle
microtubules
Aster
Sister
chromatids
Centrosome
Metaphase
Plate
Kinetochores
Overlapping
nonkinetochore
microtubules
Microtubules
Kinetochores
microtubules
0.5 µm
Chromosomes
– Attach to the
kinetochores of
chromosomes and move
the chromosomes to the
metaphase plate
Figure 12.7 Centrosome
1 µm
Separating Chromosomes
• During anaphase, sister chromatids are
separated
– Proteins that hold the chromatids together are
inactivated
– Kinetochores have motor proteins that move the
chromosomes along microtubules towards the
spindle poles
• Nonkinetochore microtubules elongate the cell
Figure 12.7 Testing a hypothesis for chromosome migration during anaphase
Model:
Chromosomes travel along
microtubules towards the poles
Microtubules shorten by
depolymerizing at their kinetochore
ends
Experiment:
Microtubules of dividing cells are
labeled with a fluorescent dye
A laser bleaches the dye in a region
midway between one spindle pole and
the chromosome
As chromosomes move towards the
poles, microtubules on the kinetochore
side of the mark shortened, while
those on the centrosome side
remained the same length
Cytokinesis : division of cytoplasm
• Animal cells : cleavage
– Cleavage furrow
• Division begin as a shallow groove in the cell surface near the
metaphase plate
– Contractile ring (on the cytoplasmic side of the furrow)
• Composes of actin microfilaments and the protein myosin
– Cleavage furrow deepens until the parent cell is
pinched in two
• Plant cells : cell plate formation
– Vesicles from the Golgi collect at the middle of the cell
producing a cell plate
– Cell wall material carried in the vesicles is deposited on
the plate as it grows, until it fuses with the membrane
along the perimeter of the cell
Figure 12.8 Cytokinesis in animal and plant cells
Figure 12.9 Mitosis in a plant cell
Chromatin
condensing
Spindle forms
Nuclear envelope
fragments
Cell
plate
forms
Microtubules capture
kinetochores
Chromosomes line up at
metaphase plate
Chromatids separate
and move towards poles
Evolution of Mitosis: prokaryotic reproduction
• Cell division by binary
fission
• Bacterial chromosome
is a single circle of DNA
• Replication of DNA
begins at a specific
origin of replication
• Duplicated
chromosomes actively
move apart without the
help of mitotic spindle
Figure 12.10 Bacterial cell division (binary fission)
Figure 12.10 Bacterial cell division (binary fission)
Figure 12.11 A hypothesis for the evolution of mitosis
Chromosomes move to opposite
ends of the cell by unknown
mechanisms
Microtubules pass through the
nucleus in cytoplasmic tunnels
Protists:
Plankton
Nuclear envelope remains intact
Chromosomes attach to envelope
Mitotic spindle form in the nucleus
Algae:
Phytoplankton
Nuclear envelope remains intact
Microtubules separate the
chromosomes
Mitotic spindle form outside of the
nucleus
Nuclear envelope breaks down
Microtubules separate the
chromosomes
Cell Cycle Regulation
• Timing and rate of cell division is critical for
normal growth, development, and maintenance
– Skin cells divide frequently
– Liver cells divide only when needed (repair)
– Muscle cells and nerve cells do not divide
• Molecular mechanisms regulate the cell cycle
• Improper cell cycle regulation can result in human
disease : cancer
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.
Figure 12.13 Mechanical analogy for the cell cycle control system
The cell cycle is regulated at certain checkpoints by both internal and external controls
Checkpoints
• Critical regulatory points where activating and
inhibiting signals can control progression through
the cell cycle
– Stop signals predominant at checkpoints until overridden
by an activating signal
• Signals come from cell surveillance mechanisms
– Informing the cell when all processes in the current
phase have been completed correctly or not
• Signals come from outside the cell
• Checkpoints
– G1 phase : restriction point
• cells that do not pass this point go into a nondividing G0 phase
– G2 phase
– M phase
Cell Cycle Control Molecules
• The fluctuation in the amount and activity of
regulatory molecules in the cytoplasm pace
the sequential events of the cell cycle
• Kinases that drive the cell cycle - Cdks
(cyclin dependent kinases)
– Present at a constant concentration in an
inactive form
– Activated by attachment to a cyclin
• Activity of Cdks rises and falls with changes
in the concentration of its cyclin partner
Figure 12.14 Molecular control of the cell cycle at the G2 checkpoint
• MPF = M phase
(maturation)
Promoting Factor
MPF causes
the
breakdown
of cyclin
MPF
promotes
mitosis
Cdk + cyclin
combine to form
MPF
– triggers the passage
past the G2 checkpoint
into M phase by
phosphorylating
proteins involved in
nuclear envelope
breakdown
– Initiates process
leading to the
destruction of its cyclin,
switching itself off and
driving the cell past the
M phase checkpoint
Signals that Regulate the Cell
Cycle
• Internal signals
– M phase checkpoint: anaphase does not
begin until all chromosomes are attached to
spindle on the metaphase plate
– Kinetochores not attached to spindle send a
signal to delay anaphase
• External signals
– Growth factors (eg: PDGF)
– Density-dependent inhibition of cell division
Figure 12.15 The effect of a growth factor on cell division
Platelet-derived growth factor (PDGF)
stimulates the division of human fibroblast cells
Figure 12.15x Fibroblast growth
Figure 12.16 Density-dependent inhibition of cell division
Density-dependent
inhibition:
A cell population reaches a
certain density, growth
factors and nutrients
available to each cell
becomes insufficient to allow
continued cell growth
Anchorage dependence:
Cells must be attached to a
substratum to divide –
signals are transmitted to
cell cycle control via plasma
membrane proteins and
elements of the cytoskeleton
linked to them
Cancer
• Cancer cells do not respond to normal cell cycle controls
and divide excessively
– Make a required growth factor themselves
– Abnormal cell cycle control system
– Abnormality in signaling pathway that conveys the growth factor
signal
• Cancer cells divide indefinitely if supplied with nutrients: in
vitro cell lines (HeLa cells)
• Transformation – the process that converts a normal cell
to a cancer cell
• Tumor – a mass of abnormal cells that have evaded the
immune system
– Benign: cell mass remains at original site
– Malignant: tumor invades organs and impairs function
• Metastasis – spread of cancer cells to locations distant
from the original site
– cancer cells can lose attachments to other cells and spread into
nearby tissues or enter the blood stream.
Figure 12.17 The growth and metastasis of a malignant breast tumor
Homework
• Text:
– Pg. 234: Self Quiz 1 - 11 (due 2/6/12)