1. Cell Division, Cell Cycle Control, and Cancer
Events in Interphase
Events in mitosis
How is the Cell Cycle controlled?
Energy requirements
Some Interesting Questions

2. Events in Interphase 1. Growth (G1) phase 2. S phase
G1 checkpoint: also called the restriction point. DNA damage monitored by p53.
2. S phase
DNA synthesis
Duplication of Chromosomes
3. Growth (G2) phase

3. p53
A tumour-suppressor protein. Sometimes called the “Guardian Angel” of the cell.
Activated by DNA damage. Once activated, p53 can induce the activation of other proteins by acting as a transcription factor.
Since p53 may induce apoptosis, maybe it also should be called the Angel of Death?!

4. p53
Mutations may inactivate p53. Alternatively, some viruses (such as HPV) produce a protein which inactivates p53.
In both cases, a loss of function occurs that may be a step in the progression of a cell to the transformed state.

5. DNA Replication Occurs during the S phase of the Cell Cycle
Replication is semi-conservative
DNA polymerase and accessory enzymes are required for DNA synthesis

6. Chromosome condensation
The protein condensin links DNA loops together during the process of
Chromosome condensation.

7. Events in Mitosis I Mitotic Spindle Forms
Centrosomes move to opposite sides of the cell
Chromosomes become condensed
Nuclear envelope fragments
Microtubules connect to the kinetochore

8. Events in Mitosis II
Chromosomes “convene” or group at the metaphase plate
Note: Homologous chromosomes do NOT pair up during mitosis.
Sister chromatids separate and the chromosomes migrate to opposite sides of the cell. Failure of sister chromatids to separate is called . . .

9. Nondisjunction
If sister chromatids of a chromosome fail to separate, both will be pulled to one pole of the cell.
One daughter cell will receive too many chromosomes while its counterpart, the other daughter cell, will receive too few chromosomes.

10. Cytoskeletal Requirements
Microtubules
Microfilaments during cytokinesis in animal cells

11. Microtubules Spindle microtubules assemble at the centrosome.
Once the nuclear envelope disassembles, some microtubules attach to the kinetochore of chromosomes
A “tug-of-war” ensues where the chromosomes move back and forth. This involves the tubulin polymerization and depolymerization which lengthens or shortens microtubules.

12. Energy requirements I ATP needed for DNA and protein synthesis
Movement of chromosomes through action of motor proteins at kinetochores
Condensin

13. Energy requirements II
Phosphorylation and dephosphorylation of proteins active in the cell cycle during
Cell Surface receptor activation
Signal transduction pathways
Nuclear membrane disassembly and assembly
Cyclin and cyclin-dependent kinase (cdk)
ATP or GTP will be needed to serve as the phosphate donor for the above phosphorylation events.

14. Some Interesting Questions
What keeps DNA from getting all tangled up as it condenses?
How do Chromosomes move?
How does the nuclear membrane just “disappear” and then reform?
What can go wrong?
What triggers a cell to start dividing?

15. Cell Growth Signals
PDGF (platelet-derived growth factor), a protein released by platelets at the site of injury, will trigger fibroblasts to divide by a series of steps that involve
1. Reception: PDGF (the ligand) binds to the PDGF receptor, which becomes activated by phosphorylation.
2. Signal transduction.
3. Response. For the fibroblast, the response will be to divide.

16. Cell cycle control Checkpoints: stop signals Go signals
Role of Tumor suppressor genes
(such as p53 and the retinoblastoma
protein-Rb)
Go signals
Proto-oncogenes: normal cellular
genes (such as ras) that activate
cell division pathways

17. Loss of Cell cycle control I
Cancer
Gain of function: proto-oncogenes mutated to a permanently active form, becoming an oncogene. (This situation is like a stuck accelerator on a car)
Loss of function: tumor-suppressor genes inactivated by mutations or the action of viruses (such as HPV). (This situation is like a broken brake on a car)

18. Loss of Cell cycle control II
Defects in DNA repair enzymes may contribute to the induction of cancer: failure in DNA repair may lead to mutations that activate proto-oncogenes or inactivate tumor suppressor genes

19. No penguins here! “I say cell division should be fast!”
Slow and steady”
“I say cell division should be fast!”