Download Cell Cycle and Mitosis

Cell Cycle and Mitosis
Cell Cycle
 Stages in growth &
division
 G1 Phase
 S Phase
 G2 Phase
 M Phase
 Cytokinesis
M
Mitosis
G2
Gap 2
S
Synthesis
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G1
Gap 1
G0
Resting
G1 Phase
First growth stage
Cell increases in size
Cell prepares to copy its DNA
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Synthesis Phase
Copying of all of DNA’s instructions
Chromosomes duplicated
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G2 Phase
Time between DNA synthesis & mitosis
Cell continues growing
Needed proteins produced
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M Phase
Cell growth & protein production stop
Cell’s energy used to make 2 daughter
cells
Called mitosis or karyokinesis (nuclear
division)
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The Cell Cycle
•Most of the cell's life is spent doing
its regular function.
•Cells divide along a rough time frame
called its Cell Cycle.
•The Cell cycle consists of the
folowing steps:
•G1 (Gap 1) Phase - Cell performs its
normal function (cells which do not
divide stay in this stage for their
entire life span)
•S (Synthesis) Phase - Here the cell
actively duplicates its DNA in
preparation for division
•G2 (Gap 2) Phase - Amount of
cytoplasm (including organelles)
increases in preparation for division.
•Mitosis - Actual division occurs
Checkpoint control system
• Checkpoints
– cell cycle controlled by STOP & GO
chemical signals at critical points
– signals indicate if key cellular
processes have been
completed correctly
Checkpoint control system
• 3 major checkpoints:
– G1/S
• can DNA synthesis begin?
– G2/M
• has DNA synthesis been
completed correctly?
• commitment to mitosis
– spindle checkpoint
• are all chromosomes attached
to spindle?
• can sister chromatids
separate correctly?
Growth Factors and Cancer
• Growth factors can create cancers
– proto-oncogenes
• normally activates cell division
– growth factor genes
– become oncogenes (cancer-causing) when mutated
• if switched “ON” can cause cancer
• example: RAS (activates cyclins)
– tumor-suppressor genes
• normally inhibits cell division
• if switched “OFF” can cause cancer
• example: p53
Cancer & Cell Growth
• Cancer is essentially a failure
of cell division control
– unrestrained, uncontrolled cell growth
• What control is lost?
– lose checkpoint stops
– gene p53 plays a key role in G1/S restriction point
p53 is the
Cell Cycle
Enforcer
• p53 protein halts cell division if it detects damaged DNA
– options:
» stimulates repair enzymes to fix DNA
» forces cell into G0 resting stage
» keeps cell in G1 arrest
» causes apoptosis of damaged cell
• ALL cancers have to shut down p53 activity
p53 discovered at Stony Brook by Dr. Arnold Levine
p53 — master regulator
gene
NORMAL p53
p53 allows cells
with repaired
DNA to divide.
p53
protein
DNA repair enzyme
p53
protein
Step 1
Step 2
Step 3
DNA damage is caused
by heat, radiation, or
chemicals.
Cell division stops, and
p53 triggers enzymes to
repair damaged region.
p53 triggers the destruction
of cells damaged beyond repair.
ABNORMAL p53
abnormal
p53 protein
Step 1
Step 2
DNA damage is
caused by heat,
radiation, or
chemicals.
The p53 protein fails to stop
cell division and repair DNA.
Cell divides without repair to
damaged DNA.
cancer
cell
Step 3
Damaged cells continue to divide.
If other damage accumulates, the
cell can turn cancerous.
Development of Cancer
• Cancer develops only after a cell experiences
~6 key mutations (“hits”)
– unlimited growth
• turn on growth promoter genes
– ignore checkpoints
• turn off tumor suppressor genes (p53)
– escape apoptosis
• turn off suicide genes
– immortality = unlimited divisions
• turn on chromosome maintenance genes
– promotes blood vessel growth
• turn on blood vessel growth genes
– overcome anchor & density dependence
• turn off touch-sensor gene
It’s like an
out-of-control
car with many
systems failing!
What causes these “hits”?
• Mutations in cells can be triggered by




UV radiation
chemical exposure
radiation exposure
heat




cigarette smoke
pollution
age
genetics
Tumors
• Mass of abnormal cells
– Benign tumor
• abnormal cells remain at original site as a
lump
– p53 has halted cell divisions
• most do not cause serious problems &
can be removed by surgery
– Malignant tumor
• cells leave original site
– lose attachment to nearby cells
– carried by blood & lymph system to other tissues
– start more tumors = metastasis
• impair functions of organs throughout body
Traditional treatments for cancers
• Treatments target rapidly dividing cells
– high-energy radiation
• kills rapidly dividing cells
– chemotherapy
• stop DNA replication
• stop mitosis & cytokinesis
• stop blood vessel growth
New “miracle drugs”
• Drugs targeting proteins (enzymes)
found only in cancer cells
– Gleevec
• treatment for adult leukemia (CML)
& stomach cancer (GIST)
• 1st successful drug targeting only cancer cells
without
Gleevec
Novartes
with
Gleevec
Cell Division
Mitosis
Mitosis
•
•
Eukaryotes divide by a more complicated system called Mitosis
This is because:
1. They have a nucleus which must be broken up and then reformed
2. They have their DNA “packaged” in the form of Chromosomes
3. Chromosomes are composed of Chromatin
1. Made of DNA Strands & Proteins
4. Also contain Nucleosomes containing Histones - Proteins the DNA is wrapped
around Name for the DNA/Protein complex is Chromatin
5. They usually have more than 1 chromosome (Humans have 23 pairs)
6. They have numerous organelles to equally share
Chromatin / Chromosomes
Interphase
• Cell Replicates its DNA/Chromosomes
in preparation of upcoming division
Animal Cell
Plant cell
• Mitosis is a continuum of changes.
– For description, mitosis is usually broken
into 4 subphases:
•
•
•
•
prophase,
metaphase,
anaphase, and
telophase.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• By late interphase, the chromosomes
have been duplicated.
• The centrosomes begin to organize
microtubules into an aster (“star”).
Fig. 12.5a
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• In prophase, the chromatin condenses into
chromosomes.
• The chromosomes are two identical
threads (sister chromatids) joined at the
centromere.
Fig. 12.5b
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• During late prophase, the nuclear
envelope fragments.
• Microtubules from the spindle interact
with the chromosomes.
Fig. 12.5c
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• Metaphase – chromosomes gather at the
midline of the cell with their
centromeres aligned on the metaphase
plate.
• Enzymes separate the
Sister chromatids.
Fig. 12.5d
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• At anaphase, the centromeres divide,
separating the sister chromatids.
• Each is now pulled toward the pole to
which it is attached by spindle fibers.
• By the end, the two
poles have equivalent
collections of
chromosomes.
Fig. 12.5e
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• At telophase, the cell continues to
elongate.
• Two nuclei begin to form, surrounded by
the fragments of the parent’s nuclear
envelope.
• Chromatin becomes
less tightly coiled.
• Cytokinesis, division
of the cytoplasm,
begins.
Fig.
12.5fas Benjamin Cummings
Copyright © 2002 Pearson Education, Inc., publishing
Fig. 12.5 left
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Fig. 12.5 right
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Prophase
Animal Cell
Plant Cell
Metaphase
Animal Cell
Anaphase
Telophase (cytokenesis)
Animal
Cell
Animal Cytokeneisis
• With animals, the
membranes pinch together
to form a Cleavage Furrow,
which eventually fuses to
form two daughter cells
Overview of Mitosis
Fig. 12.9
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings