Warm Up

1. Warm Up • Which of the following is significantly different between plant and animal cells? • Metaphase • Anaphase • Cytokinesis • Prophase • Be prepared to explain your answer.

2. Cytokinesis: A Closer Look • In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow • In plant cells, a cell plate forms during cytokinesis Animation: Cytokinesis

3. LE 12-9a 100 µm Cleavage furrow Daughter cells Contractile ring of microfilaments Cleavage of an animal cell (SEM)

4. LE 12-9b Vesicles forming cell plate Wall of parent cell 1 µm New cell wall Cell plate Daughter cells Cell plate formation in a plant cell (TEM)

5. Binary Fission • Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission • In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart

6. Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Two copies of origin LE 12-11_3 Origin Origin Replication continues. One copy of the origin is now at each end of the cell. Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. Two daughter cells result.

7. Regulation of the Cell Cycle

8. Regulation of the Cell Cycle • Frequency of cell division varies with the type of cell • Skin cells vs. muscle and nerve cells • Liver cells – reserve ability

9. Cell cycle control system • Cyclically operating set of molecules in the cell that both triggers and coordinates key events in the cell cycle. • Checkpoint – control point where stop and go signals regulate the cycle. • Report whether crucial cellular processes up to that point have been completed correctly. • Found in the G1, G2, M phases.

10. Figure 8.16 Cell-Cycle Checkpoints G2 checkpoint Pass this checkpoint if:• cell size is adequate• chromosome replication is successfully completed M Mitosis G2 Second gap Metaphase checkpoint Pass this checkpoint if:• all chromosomes are attached to mitotic spindle G1 First gap G1 checkpoint DNA synthesis Pass this checkpoint if:• cell size is adequate• nutrient availability is sufficient• growth factors (signals from other cells) are present S

11. G0 Phase • Most human body cells are in this phase. • Nerve cells • Muscle cells • Some liver cells can be called back from G0 phase in event of injury.

12. G1 checkpoint • “restriction point” most important in mammalian cells. • If G1 checkpoint is a go, cell usually completes S, G2, and M phases and divide. • If not, it will exit the cycle and switch to a non-dividing stage G0.

13. LE 12-15 G0 G1 checkpoint G1 G1 If a cell does not receive a go-ahead signal at the G1 checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state. If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

14. Cell cycle molecules 2 types of Proteins – kinases and cyclins • Kinases – enzymes that activate or inactivate other proteins by phosphorylating them. • Particular kinases give the go-ahead signals at the G1 and G2 checkpoints. • Kinase present in constant concentrations but inactive in growing cell • Must be attached to cyclin to be active

15. CDK’s • Cyclin – fluctuating concentration in the cell • = cyclin-dependent kinases (Cdks) • Cyclin must bind to these kinases to “activate” them. • Activity rises and falls with changes in the concentration of cyclin partner. • Ex: MPF – cyclin-Cdk complex discovered first. • M-phase promoting factor – triggers the cell’s passage past the G2 checkpoint.

16. Figure 8.15b Activated cyclin-dependent kinase has an array of effects. Phosphorylate chromosomal proteins; initiate M phase Activated MPF Phosphorylate microtubule- associated proteins. Activate mitotic spindle? CdK CdK Phosphorylate an enzyme that degrades cyclin; cyclin concentrations decline + Cyclin Cyclin-dependent kinase

17. Cyclin concentrations regulate MPF activity. M phase M phase MPF activity Cyclinconcentration Time

18. LE12-16b G1 Cyclin S Cdk M Degraded cyclin G2 accumulation G2 checkpoint Cdk Cyclin is degraded Cyclin MPF Molecular mechanisms that help regulate the cell cycle

19. Check In with group • What is a checkpoint? • What is the purpose/value of checkpoints?

20. When cyclins accumulate during G2 with Cdks -> initiates mitosis. • Phosphorylates other proteins • Activates other kinases • Promotes fragmentation of nuclear envelope during prometaphase • Contributes to signals for chromosome condensation • In anaphase, helps switch itself off my initiating destruction of its own cyclin. Cdk persists in inactive form until new cyclin is synthesized in S and G2 phase of the next cycle.

21. Stop and go signs • Internal signal at M phase checkpoint: • Anaphase delayed until all chromosomes are properly attached to the spindle at the metaphase plate. • Kinetochores not yet attached to spindle send a molecular signal that causes the sister chromatids to stay together. • This ensures that daughter cells do not end up with missing or extra chromosomes.

22. External chemical factors • Both chemical and physical external factors influence cell division. • Cells fail to divide if an essential nutrient is left out. • For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture.

23. External physical factor • Density-dependent inhibition – crowded cells stop dividing. • Cultured cells normally divide until they form a single layer of cells on the inner surface of container. • If some cells removed, cells bordering open space begin dividing again until vacancy is filled. • Anchorage dependence – cells must be attached to substratum in order to divide.

24. Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). LE 12-18a If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). 25 µm Normal mammalian cells

25. Cancerous Cells • Given what you know about the cell cycle, what do you think might lead to a cell becoming cancerous?

26. Cancer and the Cell Cycle • Cell cycle not regulated in cancer • Mutations of genes that regulate cell cycle. • Mitosis is uncontrolled, so many cells form. • Cells do not die (~50 “splits”) like normal. A cancer cell can last indefinitely

27. Loss of Cell Cycle Controls in Cancer Cells • Cancer cells do not respond normally to the body’s control mechanisms • Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue

28. Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. LE 12-18b 25 µm Cancer cells

29. Tumors • If abnormal cells remain at the original site, the lump is called a benign tumor • Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form secondary tumors

30. LE 12-19 Lymph vessel Tumor Blood vessel Glandular tissue Metastatic tumor Cancer cell A small percentage of cancer cells may survive and establish a new tumor in another part of the body. Cancer cells invade neighboring tissue. A tumor grows from a single cancer cell. Cancer cells spread through lymph and blood vessels to other parts of the body.

31. Inheriting Cancer depends on type of cell with mutation 1) Somatic Cells – the cells of your body • A mutation cannot be passed on. 2) Germ Cells – Reproduction Cells (egg and sperm) • A mutation will be passed on.

32. Mutations in genes that control cell growth can cause cancer • Oncogenes: stimulate mitosis and tumor formation even without growth signals • Example- Growth factor receptor genes • Tumor suppressor genes: normally prevent mitosis and tumor formation. If mutated, do not stop a tumor. • Examples- p53 gene BRCA1 gene

33. Causes of cancer • Mutagens - substances that cause mutations (changes in DNA sequence) • Carcinogen – cancer causing substance • Rare, random chance