1. Cell Growth & Division Control of Cell Cycle | Disruptions to Cell Cycle

2. Learning Objectives Discuss control of the cell cycle Analyze how disruptions to the cell cycle can lead to cancer The Cell Cycle

3. DNA replication control: – Genes provide instructions for DNA replication process – Proteins find and repair mistakes in DNA Cell cycle checkpoints: – Chemical signals tell cycle to continue or stop Control of the Cell Cycle

4. Cells enter resting phase (G 0 ) after G 1 in the absence of a continue signal Contact inhibition can occur when neighboring cells touch, sending signals to halt cell division Control of the Cell Cycle

5. Intracellular Controls: 1. Checkpoints: Specific sites in the cycle that monitor the progress of cell division. Intracellular Controls: a. G 1 Checkpoint: “Restriction Point” in animal cells, “Start” in yeast cell. Assesses environmental conditions b. G 2 Checkpoint: Triggers start of M Phase c. M Checkpoint: Assesses mitosis Cell Cycle Control

6. Extracellular Controls: 1. Mitogens: Stimulate cell division by relieving negative controls “Release the brakes” (release Cdks) Primarily in G 1 Stage Responds to growth signals Examples: PDGF (Platelet Derived Growth Factor) EGF (Epidermal Growth Factor) Extracellular Controls: 2. Growth Factors: Bind to receptors on the cell membrane surface and activate intracellular signaling. 3. Survival Factors: Signals from other cells preventing apoptosis. Competition (cells with enough SF continue living) Cell Cycle Control

8. Intracellular Controls: Cyclins: Proteins that undergo synthesis & degradation in each cell cycle Cyclin Dependent Kinases (Cdk’s) Proteins that activate or suppress Inactive until bound to a CYCLIN Express their activity at the various “checkpoints” by adding PO 4 group Cell Cycle Control

9. Checkpoint video Cell Cycle Control

10. Mutations – a mistake in the replication of DNA Inherited mutations cause genetic diseases Mutations accumulated during a lifetime cause disruptions in protein production or the cell cycle Disruptions to the Cell Cycle

11. Specific genes act as molecular switch checkpoints – Activation of these genes regulates mitosis and cell division – Mutations in these genes can cause checkpoint malfunctions Proto-oncogenes – the genes which control the timing of cell division – Oncogene – the genes that instruct unlimited division Results from mutation in a proto-oncogene Tumor suppressor genes – the genes which suppress abnormal cell growth – Contain instructions for cell repair and death – Mutations allow cells to divide uncontrollably Disruptions to the Cell Cycle

12. G 1 Checkpoint:  Called “Restriction Point” in animal cells  Multiple control factors required Cyclin & G 1 Cdk “Rb Protein” (Retinoblastoma) “P 53 Protein” Proto-oncogenes vs. Oncogene

13. Rb Protein: Blocks S Phase Influenced by external factors P 53 Gene: “Guardian Angel gene” Assesses DNA Prevents S Phase if DNA inaccurate Allows time for repair & correction Severe DNA damage  apoptosis “Better dead than read” Cell Cycle Control

14. 14 Regulation at the G1 Checkpoint Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. a. P P RB protein RB protein E2F CDK not present E2F not released released E2F E2F binds to DNA. DNA cell cycle proteins phosphorylated RB CDK present b. P P P P breakdown of p53 no DNA damage DNA damage phosphorylated p53 DNA repair proteins apoptosis p53 binds to DNA. DNA p53

15. Tumor – an uncontrolled growth of cells – Benign – a localized tumor which usually does not cause disease – Malignant – a type of tumor in which the cells tend to invade and spread throughout the body – Cancer – a disease in which malignant cells invade and destroy body tissues Disruptions to the Cell Cycle

16. Carcinogens – the types of radiation, viruses, or chemicals known to cause cancer – stimulate cancer development by damaging DNA Disruptions to the Cell Cycle