1. The Cell Cycle

2. Why It Matters Cell division:
Is what got you to your present station in life
25,000,000/second (hair, skin, blood cells, tissue repair, etc.)
Body cannot give cells the license to decide on their own when to grow & divide

3. Cancers: failures of cell cycle
The molecular actions of most oncogenes
& tumor suppressor genes must be explained in terms
of their effects on the cell cycle…

4. Central Governor of Growth & Proliferation
Cell cycle clock is a molecular circuitry that:
Processes/integrates signals from outside & inside the cell
Decides whether a cell should enter active cell cycle or retreat to non-proliferating state

5. So, let’s make a new cell! Key processes: DNA replication
Mechanism to separate replicated chromosomes
Set of molecular controls over entire process
A cast of thousands!
(mostly proteins)

6. Phases of cell cycle Interphase:
Gap 0 (G0): resting phase; no division (e.g., neurons)
G1: growth, prep for DNA synthesis (e.g., enzymes)
S: DNA replication
G2: growth, prep for ÷
M phase:
Mitosis: nuclear ÷
Cytokinesis: cytoplasmic ÷

7. Phases of Mitosis Mitosis Prophase Metaphase Anaphase Telophase
Cytokinesis

8. Regulation of cell cycle
Checkpoints monitor & regulate the progress of the cell cycle and impose quality control
Cells undergoing cell cycle are targeted in cancer therapy (DNA is relatively exposed)

9. The Restriction point (R G1/S transition Deregulation of the R point decision accompanies the formation of most, if not all types of cancer

10. Cyclins & cyclin-dependent kinases (cdks)
Cyclins: proteins that regulate activity of cdks
Cdks: enzymes that control the cell cycle
Kinases specialize in phosphorylation cascades
cdks: serine/threonine kinases

11. Pattern of cyclin-cdk activity
Cyclin D: 1st cyclin produced (in response to growth factors); binds to cdks 4/6 Cdks phosphorylate t target proteins (+ or –)

12. Retinoblastoma protein (pRb) & G1-S transition
pRb controls passage through R point
Cyclin D-cdks 4/6 phosphorylates pRb which then activates transcription factor(TFs), proteins involved in “turning on” genes (e.g., other cyclins DNA polymerase, etc).

13. Transcription Factors (TFs)
There are TFs in human genome
genes are turned on over the course of the cell cycle!

14. Cancer & pRb pRb function can be impacted or lost in a variety of ways
Excessive mitogenic signals
Mutation of the Rb gene
Action of oncoproteins that deregulate pRb phosphorylation

15. DNA mutations disrupt the cell cycle
Mutations may be caused by:
1. radiation
2. smoking
3. Pollutants
4. chemicals
5. viruses

16. While normal cells will stop dividing if there is a mutation in the DNA, cancer cells will continue to divide with mutation

17. Treating Cancers
Cancer treatments include drugs that can stop cancer cells from dividing.