chapter 12: cell cycle. chromosome sorting the goal of cell division typically is to equally...
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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 DifferencesProkaryote Chromosome Eukaryote Chromosome
Here “chromosome”and “DNA” are not100% synonymous
Chromosomes vs. Chromatin• Chromosomes
• Tightly packaged DNA• Found only during cell
division• DNA is not being used for
macromolecule synthesis
• Chromatin
• 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 ofprotein
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
Chromosome
Chromatid
Sister Chromatids
Eukaryotic Chromosome
Genome = DNA
Chromosomes = DNA + PROTEIN(visible under light
microscope)
Chromatin = DNA + PROTEIN
(unwound)DNA
Important Vocabulary
• Centromere• Centrosome• Centriole• Kinetochore• Kinetochore microtubules• Mitotic spindle• Nonkinetochore microtubules• Spindle apparatus• Spindle fibers
Important Vocabulary
• Centromere• Centrosome• Centriole• Kinetochore• Kinetochore microtubules• Mitotic spindle• Nonkinetochore microtubules• Spindle apparatus• Spindle fibers
Nonmembranous organelles that
organize microtubules
throughout the cell cycle
2 Centrioles = Centrosome
Important Vocabulary
• 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
• Centromere• Centrosome• Centriole• Kinetochore• Kinetochore microtubules• Mitotic spindle• Nonkinetochore microtubules• Spindle apparatus• Spindle fibers
Attachment point on Chromatids for
spindle fiber
Important Vocabulary
• 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
• 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
• 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
• 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
• 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– 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– Attach to the
kinetochores of chromosomes and move the chromosomes to the metaphase plate
CentrosomeAster
Sisterchromatids
MetaphasePlate
Kinetochores
Overlappingnonkinetochoremicrotubules
Kinetochores microtubules
Centrosome
ChromosomesMicrotubules0.5 µm
1 µm
Figure 12.7
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
Spindle forms
Nuclear envelope fragments
Microtubules capture kinetochores
Chromosomes line up at metaphase plate
Chromatids separate and move towards
poles
Cell plate forms
Chromatin condensing
• 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
Evolution of Mitosis: prokaryotic reproduction
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
Mitotic spindle form outside of the nucleus
Nuclear envelope breaks down
Microtubules separate the chromosomes
Mitotic spindle form in the nucleus
Nuclear envelope remains intact
Microtubules separate the chromosomes
Microtubules pass through the nucleus in cytoplasmic tunnels
Nuclear envelope remains intact
Chromosomes attach to envelope
Chromosomes move to opposite ends of the cell by unknown mechanisms
Protists: Plankton
Algae: Phytoplankton
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 cycleIn each experiment, cultured mammalian cells at two different phases of the cell cycle were induced to fuse.
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.
EXPERIMENTS
RESULTS
CONCLUSION The results of fusing cells at two different phases of the cell cycle suggest that molecules present in the cytoplasm of cells in the S or M phase control the progression of phases.
When a cell in the S phase was fused with a cell in G1, the G1 cellimmediately entered the S phase—DNA was synthesized.
S
S S M M
MG1 G1
Experiment 1 Experiment 2
Figure 12.13 A, B
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– 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
Cdk + cyclin combine to form MPF
MPF causes the
breakdown of cyclin
MPF promotes mitosis
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)
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