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

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

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

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

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

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

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

Checkpoint video Cell Cycle Control

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

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

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

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 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

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

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