In the early 1970s, a variety of experiments led to the hypothesis that the cell cycle is driven by...
12
In the early 1970s, a variety of experiments led to the hypothesis that the cell cycle is driven by specific signaling molecules present in the cytoplasm. Experiment 1 Experiment 2 S S S G 1 G 1 M M M EXPERIMENT RESULTS When a cell in the S phase was fused with a cell in G 1 , the G 1 nucleus immediately entered the S phase—DNA was synthesized. When a cell in the M phase was fused with a cell in G 1 , the G 1 nucleus immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.
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Transcript of In the early 1970s, a variety of experiments led to the hypothesis that the cell cycle is driven by...
In the early 1970s, a variety of experiments led to the hypothesis that the cell cycle is driven by specific signaling molecules present in the cytoplasm.
Experiment 1 Experiment 2
S
S S
G1 G1M
M M
EXPERIMENT
RESULTS
When a cell in the Sphase was fusedwith a cell in G1,the G1 nucleusimmediately enteredthe S phase—DNAwas synthesized.
When a cell in the M phase was fused witha cell in G1, the G1
nucleus immediatelybegan mitosis—a spindleformed and chromatincondensed, even thoughthe chromosome had notbeen duplicated.
Cell Cycle Control Cell cycle control system: a cyclically
operating set of molecules in the cell that both triggers and coordinates key events in the cell cycle.
The cell cycle is regulated at certain checkpoints by both internal and external signals.
A checkpoint is a control point in the cell cycle where stop and go-ahead signals can regulate the cycle.
Cyclins and Cyclin-Dependent Kinases
Cell cycle regulatory molecules are mainly proteins of two types: kinases and cyclins. Kinases are enzymes that activate or inactivate
other proteins by phosphorylating them. Most cell cycle kinases stay at a constant
concentration in the cell. Cell cycle cyclins have fluctuating concentrations
in the cell. To be active, cell cycle kinases must be
attached to a cyclin (cyclin-dependent kinase or Cdk).
MPF as a Cdk
Internal CheckpointsProtein Location Purpose
Ras cyclin G1 checkpoint Checks that cells are big enough to enter the next part of cell cycle.
P53 G1 checkpoint Inspects chromosomes for damage.
ATM/Nibrin S checkpoint Inspects copied DNA for mistakes.
MPF G2 checkpoint Phosphorylates proteins, which initiates mitosis.
MAD1 Metaphase Checks that spindle fibers are attached to chromatids.
External Checkpoints
Growth factor: protein releases by certain cells that stimulates other cells to divide.
Density-dependent inhibition: crowded cells stop dividing. Binding of a cell-surface protein to an adjoining
cell sends a cell division-inhibiting signal. Anchorage dependence: cells must be
attached to substratum to divide.
Loss of Cell Cycle Controls in Cancer Cells
Cancer cells do not stop dividing when growth factors are depleted. Hypothesis: cancer cells do not need growth
factors in their culture medium to grow. Hypothesis: cancer cells have an abnormal cell
cycle control system. The underlying basis of the abnormality is
almost always a change in one or more genes that alters the function of their protein products, resulting in faulty cell cycle control.
HeLa cells (green microtubles and orange Golgi)
If a cancer cell stops dividing, it occurs at a random point in the cycle.
Cancer cells can go on dividing indefinitely in culture with a continual supply of nutrients. Cells are said to have undergone transformation.
Cancer cells evade the normal controls that trigger a cell to undergo apoptosis when something is wrong.
Lung cancer cell dividing.
Development of CancerCancer develops only after a cell experiences ~6 key mutations (“hits”).
Unlimited Growth Turn on growth promoter genes.
Ignore CheckpointsTurn off tumor suppressor genes (p53).
Escape ApoptosisTurn off suicide genes.
Immortality = unlimited divisionsTurn on chromosome maintenance genes.
Promotes blood vessel growthTurn on blood vessel growth genes.
Overcome anchor and density dependenceTurn off touch-sensor gene.
It’s like anout of controlcar!
p53 Mutation Controls G1 phase; tells cell to kill itself
(apoptosis) if DNA damage cannot be repaired.
Prevents development of mutated cells. Mutation in gene allows cancer cells to
continue dividing.
p53 is theCell CycleEnforcer
DNA damage is causedby heat, radiation, or chemicals.
p53 allows cellswith repairedDNA to divide.
Step 1
DNA damage iscaused by heat,radiation, or chemicals.
Step 1 Step 2
Damaged cells continue to divide.If other damage accumulates, thecell can turn cancerous.
Step 3p53 triggers the destruction of cells damaged beyond repair.
ABNORMAL p53
NORMAL p53
abnormalp53 protein
cancercell
Step 3The p53 protein fails to stopcell division and repair DNA.Cell divides without repair todamaged DNA.
Cell division stops, and p53 triggers enzymes to repair damaged region.
Step 2
DNA repair enzymep53protein
p53protein
p53: Master Regulator Gene
How does cancer happen?
Benign tumor: abnormal cells remain at the original site because they have too few genetic and cellular changes to survive at another site.
Malignant tumor: cells whose genetic and cellular changes enable them to spread to new tissues and impair functions of one or more organs.
Breast cancer cell
