Bio 201 1st Edition Lecture 26Outline of Last Lecture I. ProliferationII. The Cell CycleA. Interphase vs. MB. Frogs and The Cell CycleIII. Maturation Promoting FactorOutline of Current LectureI. The Cell Cycle CheckpointsA. Tumor Suppressor GenesB. Cell DeathC. OncogenesD. Leading to CancerCurrent LectureI. The Cell Cycle Checkpoints- Control mechanisms used by cells to ensure that cell proliferation occurs only when certain external and internal conditions are met.-G2/M checkpoint- Check cell size and DNA damage-Spindle Assembly Checkpoint- In M, checks for alignment and tensionG1/S Checkpoint- Cell size, DNA damage, environmental factors- When these checkpoints fail it can lead to cancer. Over 200 different diseases, characterized by overproliferation of cells. Main causes; Mutations in multiple genes-tumor suppressor, proto-oncogene, DNA repair genes or Infection- Oncogenes. These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.A. Tumor Suppressor Genes- Genes whose normal products inhibit cell cycle. Loss-of-function mutations inactivate protein, causing progression through cell cycle inappropriately. Examples) retinoblastoma, p53. -Retinoblastoma- Cancer of the retina, in your eye. Also the name of the gene, and the protein product of the gene that when mutated causes cancer. Rb keeps cells from proliferating in the absence of growth factors at G1/S checkpoint. Rb binds to transcription factor E2F, preventing transcription of S-phase genes. Mutations don’t turn off E2F. -p53- Named from molecular weight of 53 kDa. Mutations or deletion in p53 gene are found in 50% of all human cancers. This prevents cell cycle progression at multiple checkpoints. Mutations cause constitutive cell cycle progression. Damage of DNA Phosphorylation of p53. p53 can lead to cell suicide, which can be an active and controlled process essential for normal organismal development (fingers and toes).B. Types of Cell Death-Necrosis- Cell death due to active damage or disease; uncontrolled release of cell contents triggers massive inflammation, can damage surrounding cells in multicellular organisms. -Programmed Cell Death/ Apoptosis- Controlled cell suicide whereby cellular contents are actively degraded and cell remains are cleared by macrophage. Cell shrinkage, DNA laddering, loss of membrane asymmetry and cell permeabilization. DNA laddering- During apoptosis, endonucleases digest exposed DNA between nucleosomes. This leads to fragments of DNA in multiples of about 150 base pairs. Loss of Membrane Assymetry- Normal- membrane asymmetry maintained by flipases. Apoptosis- Flipase degrade by protease, phosphotidylserine- phospholipid that’s becomes exposed when flipase degrades. C. Oncogenes- Genes whose normal protein products activate cell progression inappropriately, often from viruses. Ex) E7 HPV-Proto-oncogenes- Cellular genes whose normal protein products promote cell cycle progression, but are only active when the cell is ready and circumstances are appropriate. Ex) ras cancerD. Leading to Cancer-Tumor suppressor genes ensure that the cell cycle doesn’t proceed unless checkpoint criteria are met. Mutations allow the cell cycle to proceed regardless of whether these criteria are met. -Oncogenes causes proliferation regardless whether checkpoint criteria are met. -Proto-oncogenes are normal genes that cause uncontrolled cell proliferation when mutations cause them to be constitutively activated. -Any time checkpoint criteria are not met, cells may accumulate DNA damage and more mutations leading to
View Full Document
Unlocking...