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Frequency of Cell Division
• Varies from cell to cell
– Skin cells divide frequently
– Liver cells only when needed
– Nerve & muscle cells do NOT divide
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
What drives the cell cycle?
• The cell cycle is driven
by specific molecular
signals present in the
cytoplasm
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cell cycle control system
• Molecules in the cell trigger and coordinate key
events in the cell cycle
• Compared to the control system on an
automatic washing machine
• Cell cycle is regulated at certain checkpoints by
both internal and external controls
• Checkpoint = critical control point where stop &
go ahead signals are given
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Checkpoints
• G1, G2, and M phases
• G1 is the most important “restriction point”
– If the go ahead signal is given the cell usually
completes S, G2 and M phases
– If the go ahead signal is NOT given it enters
into a nondividing state called G0
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 12.14 Mechanical analogy for the cell cycle
control system
G1 checkpoint
Control
system
G1
M
M checkpoint
G2 checkpoint
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
G2
S
Figure 12.15 The G1 checkpoint
G0
G1 checkpoint
G1
(a) If a cell receives a go-ahead signal at
the G1 checkpoint, the cell continues
on in the cell cycle.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
G1
(b) If a cell does not receive a go-ahead
signal at the G1checkpoint, the cell
exits the cell cycle and goes into G0, a
nondividing state.
Regulatory molecules of the cell cycle
• Kinases and cyclins
• Proteins kinases give the go ahead signals at
the G1 & G2 checkpoints by phosphorylation
• These kinases are always present but in order
to be active they must be attached to a cyclin
• Called Cyclin Dependent kinases (Cdks)
• Fluctuation of MPF (M-phase promoting factor)
• Both Cdk and cyclin are needed to get past the
G2 checkpoint
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
(a) Fluctuation of MPF activity and
cyclin concentration during
the cell cycle
Relative Concentration
Figure 12.16 Molecular control of the cell cycle at
the G2 checkpoint
G1 S G2 M
MPF activity
G1 S G2 M
Cyclin
Time
(b) Molecular mechanisms that
help regulate the cell cycle
1 Synthesis of cyclin begins in late S
phase and continues through G2.
Because cyclin is protected from
degradation during this stage, it
accumulates.
5 During G1, conditions in
the cell favor degradation
of cyclin, and the Cdk
component of MPF is
recycled.
Cdk
Degraded
Cyclin
Cyclin is
degraded
4 During anaphase, the cyclin component
of MPF is degraded, terminating the M
phase. The cell enters the G1 phase.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
G2
Cdk
checkpoint
MPF
Cyclin
2 Accumulated cyclin molecules
combine with recycled Cdk molecules, producing enough molecules
of MPF to pass the G2 checkpoint and
initiate the events of mitosis.
3 MPF promotes mitosis by phosphorylating
various proteins. MPF‘s activity peaks during
metaphase.
Other factors affecting cell division
• Growth factors – a protein that is released by
certain cells that stimulate other cells to divide
• Density-dependent inhibition – when it gets too
crowded cells will stop dividing because there
is not enough nutrients to support more
• Anchorage dependence – cells must be
attached to something in order to divide
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Loss of cell cycle control – Cancer cells
• Cancer cells do not respond normally to the
body’s control mechanisms
– Do not exhibit density-dependent inhibition
– Do not stop growing when growth factors are
depleted
• Why??
– Maybe they don’t need growth factors or make
their own, abnormality in the checkpoints are
some of the hypothesis
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cancer in the body
• Transformation – converts a normal cell into a
cancer cell
• Normally our body recognizes it & destroys it
but sometimes they evade destruction, multiply
and form a tumor (mass or lump)
• If the cells remain at the original site the mass
is said to be benign
• If the cells move & cause organ damage it is
said to be malignant
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Malignant tumor cells
• Abnormal in many ways
– Unusual number of chromosomes
– Metabolisms are disabled
– Lose or destroy attachments to neighbor cells
– Secrete signals that cause blood vessels to
grow toward them
– Some can travel in blood and lymph to other
parts of the body (metastasis)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Treatment of cancer cells
• Localized tumors – radiation (damages DNA in
cancer cells more than normal cells)
• Metastatic tumors – chemotherapy is used
(drugs that are toxic to actively dividing cells)
– Taxol – freezes the mitotic spindle by
preventing microtubule depolymerization which
stops actively dividing cells from going past
metaphase
– Sickness, hair loss, nausea result from these
drugs effects on healthy cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings