The cell cycle

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The cell cycle
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The cell cycle
The life of a cell from its formation to its
division
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The cell cycle

• The big picture
• A walk through the cell cycle
• Control of the cell cycle
• Cancer a lack of control of the cell cycle

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The big picture

• Every cell from a cell-Rudolf Virchow
• The continuity of life is based on reproduction
  of cells, cell division
• Cell division results in genetically identical
  daughter cells
• Unicellular organisms use cell division as a
  means of reproduction (asexual reproduction)
• Sexually reproducing organisms develop from a
  fertilized egg via cell division
• In multicellular organisms, cell division is
  critical to growth and repair

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A walk through the cell cycle

• What happens?
• DNA, which is arranged in chromosomes, duplicates
• Each daughter cell receives the full genome
• Cytoplasm divides

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A walk through the cell cycle Prokaryotes

• Cell division begins when the chromosome begins
  to divide
• One copy moves to one pole, the other copy moves
  to other end of the cell
• The cell elongates
• Replication of the DNA is completed, the plasma
  membrane moves inward and the cell wall develops
• This is asexual reproduction (binary fission)

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A walk through the cell cycle Prokaryotes
This process is more complicated in eukaryotes

• Cell division begins when the chromosome begins
  to divide
• One copy moves to one pole, the other copy moves
  to other end of the cell
• The cell elongates
• Replication of the DNA is completed, the plasma
  membrane moves inward and the cell wall develops
• This is asexual reproduction (binary fission)

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A walk through the cell cycle Eukaryotes

• The cell cycle involves
• Interphase
• Growth and DNA duplication
• M-phase
• Mitosis-division of the nucleus
• Cytokinesis-division of the cytoplasm

DNA molecules
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A walk through the cell cycle Eukaryotes

• The cell cycle involves
• Interphase
• Growth and DNA duplication
• M-phase
• Mitosis-division of the nucleus
• Cytokinesis-division of the cytoplasm

DNA molecules
Lets watch a movie about this!
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A walk through the cell cycle Duplication of
genetic information during eukaryotic cell
division

• Interphase
• The cell grows during G1
• The chromosomes are duplicated during S phase
• Unlike proks, they have many!
• When the cell is not dividing (even as it
  duplicates its DNA) the chromosomes are long and
  thin
• After duplication the chromosomes are shorter and
  thicker
• Each duplicated chromosome has two identical
  sister chromatids (attached at the centromere)
• Each will become a chromosome in the new daughter
  cells

0.5 µm
Chromosomes
DNA molecules
Chromosome duplication (including DNA synthesis)
Centromere
Separation of sister chromatids
Sister chromatids
Centromere
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A walk through the cell cycle G2 phase
(Interphase)
During the G2 phase of interphase -Nuclear
envelope is still intact (nucleoli are still
visible) -Centrosomes have formed -Duplicated
chromosomes cannot be seen
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A walk through the cell cycle Mitosis
Prophase -Chromosomes condense and are visible
(nucleoli disappear) -Mitotic spindle begins to
form (contains centrosomes, aster, and
microtubules) -Centrosomes move away from each
other
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A walk through the cell cycle Mitosis
Prometaphase -The nuclear envelope
fragments -Microtubules attach to the chromatids
(at the kinetochores) -Chromosomes are jerked
back and forth -Other microtubules interact
(connecting from different poles)
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A walk through the cell cycle Mitosis
Metaphase -Centrosomes are now at opposite
poles -Chromosomes are lined up on the metaphase
plate -All chromosomes are attached to each of
the poles
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A walk through the cell cycle Mitosis
Anaphase -The connection between chromatids at
the centromere is cleaved (each chromatid is now
a chromosome) -Chromosomes are pulled to opposite
poles -The cell elongates -Anaphase ends when
the chromosomes reach the poles
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A walk through the cell cycle Mitosis
Telophase -Two daughter nuclei form in the cell
(nuclear envelope forms and nucleoli
appear) -Chromosomes become less dense -Mitosis
is complete
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A walk through the cell cycle Cytokinesis
Cytokinesis -Usually occurs during late
telophase -In animal cells, it occurs by
cleavage -A cleavage furrow forms -Actin
microfilaments and myosin motor
proteins cause it to contract
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A walk through the cell cycle Cytokinesis
Cytokinesis -Usually occurs during late
telophase -In plant cells, the cell wall must be
constructed -cell plate is formed -it develops
into a cell wall
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A walk through the cell cycle In review

• The cell cycle involves
• Interphase
• Growth and DNA duplication
• M-phase
• Mitosis-division of the nucleus
• Cytokinesis-division of the cytoplasm

DNA molecules
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Control of the cell cycle

• Some cells divide more than others
• Timing and rate of cell division are highly
  regulated

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Control of the cell cycle

• Some cells divide more than others
• Timing and rate of cell division are highly
  regulated

How is the cell cycle regulated?
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Control of the cell cycle

• Evidence for cytoplasmic signals (Johnson and Rao
  1970)

EXPERIMENT
Experiment 1
Experiment 2
S
G1
M
G1
RESULTS
M
S
M
S
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Control of the cell cycle
Protein kinases- enzymes that can activate or
inactivate other proteins by phosphorylating them
(Moreno et al. 1989)
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Control of the cell cycle

• The sequential events of the cell cycle are
  directed by a distinct cell cycle control system
• There are checkpoints where the cell cycle stops
  until a go-ahead signal is received
  (cyclin-dependent kinases are involved with these
  check points)
• Ie. If the cell does not get the go ahead at the
  G1 check point, it will enter a non-dividing
  phase (G0)

G1 checkpoint
Control system
S
G1
G2
M
M checkpoint
G2 checkpoint
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Control of the cell cycle

• The sequential events of the cell cycle are
  directed by a distinct cell cycle control system
• There are checkpoints where the cell cycle stops
  until a go-ahead signal is received
  (cyclin-dependent kinases are involved with these
  check points)
• Ie. If the cell does not get the go ahead at the
  G1 check point, it will enter a non-dividing
  phase (G0)
• Ie. M check point involves the connection of all
  chromosomes to the spindle (internal control)

G1 checkpoint
Control system
S
G1
G2
M
M checkpoint
G2 checkpoint
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Control of the cell cycle

• External signals
• Cell may not divide if an essential nutrient is
  lacking
• Growth factors (molecules released from other
  cells or tissues can stimulate division)
• Density-dependent inhibition-crowded cells stop
  dividing
• Anchorage dependence-to divide cells must be
  attached to a substrate

Anchorage dependence
Density-dependent inhibition
Density-dependent inhibition
25 µm
25 µm
(b) Cancer cells
(a) Normal mammalian cells
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Control of the cell cycle

• External signals
• Cell may not divide if an essential nutrient is
  lacking
• Growth factors (molecules released from other
  cells or tissues can stimulate division)
• Density-dependent inhibition-crowded cells stop
  dividing
• Anchorage dependence-to divide cells must be
  attached to a substrate

Anchorage dependence
Density-dependent inhibition
Density-dependent inhibition
25 µm
25 µm
(b) Cancer cells
(a) Normal mammalian cells
Cancer cells do not exhibit density-dependent
inhibition or anchoring dependence
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Cancer A loss of control of the cell cycle

• Cancer cells divide excessively invading other
  tissues, they can lead to death
• Why?
• Some make their own growth factors
• Some can divide without growth factors
• They lack density-dependent inhibition and
  anchorage dependence

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Cancer A loss of control of the cell cycle

• The disease begins with transformation-the
  process of converting a normal cell to a cancer
  cell
• If the transformed cell avoids the immune system
  it may proliferate and form a tumor
• A tumor can be benign or malignant (invasive
  enough to impair other organs)
• Cells in malignant tumors may have
• Unusual chromosome numbers
• Changes on the cell surface that allow them to
  spread
• Cause blood vessels to grow near them

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The cell cycle

• You should understand
• The importance of cell division
• The phases of the cell cycle interphase,
  mitosis, and cytokinesis
• Factors that control the cell cycle molecules
  involved, checkpoints, internal and external
  controls
• Cancer cells have lost control of the cell cycle