1. Frequency of Cell Division
Varies from cell to cell
Skin cells divide frequently
Liver cells only when needed
Nerve & muscle cells do NOT divide

2. What drives the cell cycle?
The cell cycle is driven by specific molecular signals present in the cytoplasm

3. 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

4. G1 is the most important “restriction point”
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

5. Figure 12.14 Mechanical analogy for the cell cycle control system
G2 checkpoint
M checkpoint
G1 checkpoint G1 S G2 M

6. Figure 12.15 The G1 checkpoint
(a) If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues      on in the cell cycle.
(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.

7. 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

8. Figure 12.16 Molecular control of the cell cycle at the G2 checkpoint
MPF promotes mitosis by phosphorylating various proteins. MPF‘s activity peaks during metaphase. 3
During G1, conditions in the cell favor degradation
of cyclin, and the Cdk component of MPF is recycled. 5
During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G1 phase. 4 2
Synthesis of cyclin begins in late S phase and continues through G2. Because cyclin is protected from degradation during this stage, it accumulates. 1
Cdk
G2 checkpoint
Cyclin
MPF
Cyclin is degraded
Degraded Cyclin G1 G2 S M
MPF activity
Time
(a) Fluctuation of MPF activity and cyclin concentration during
the cell cycle
(b) Molecular mechanisms that help regulate the cell cycle
Relative Concentration
Accumulated cyclin molecules
combine with recycled Cdk mol-
ecules, producing enough molecules of MPF to pass the G2 checkpoint and initiate the events of mitosis.

9. 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

10. 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

11. 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

12. 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)

13. 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