2. The Cell Cycle: CELLULAR REPRODUCTION What must happen before a cell can divide (reproduce)?

3. Bacterial cell division (binary fission)

4. What is different about a eukaryotic cell? What complicates eukaryotic cell division?

5. Figure 12.2 Eukaryotic chomosomes

7. Figure 12.3 Chromosome duplication and distribution during mitosis

8. Figure 12.0 Mitosis

9. The functions of Mitotic cell division: 1.) Reproduction Asexual reproduction of a unicellular, eukaryotic organism

10. 2.) Development

11. 3.) Tissue renewal in adults

12. Figure 12.4 The cell cycle

13. Figure 12.5 The stages of mitotic cell division in an animal cell: G 2 phase; prophase; prometaphase

14. Figure 12.5 The stages of mitotic cell division in an animal cell: metaphase; anaphase; telophase and cytokinesis.

15. Figure 12.6 The mitotic spindle at metaphase

16. Testing a hypothesis for chromosome migration during anaphase

17. Figure 12.8 Cytokinesis in animal and plant cells http://www.youtube.com/watch?v=KE2VI7tDL1k&feature=f vwrel

18. Figure 12-09x Mitosis in an onion root

19. Figure 12.11 A hypothesis for the evolution of mitosis

20. Evidence for cytoplasmic chemical signals in cell cycle regulation Regulation of the Cell Cycle

21. Mechanical analogy for the cell cycle control system

22. Cell Regulation- - Both internal and external signals Is the environment ok? Did all the DNA replicate? Are chromosomes intact? Many factors regulate and trigger the cell to cycle. Some cells stop dividing (neurons) some constantly divide- skin cells constantly divide

23. Regulatory proteins Protein kinases- phosphorylate targets to activate or inactive- affect cell cycle progression Cyclins- amount changes cyclically, needed to activate kinases (cdks)

24. Molecular control of the cell cycle at the G 2 checkpoint MPF- controls G2 check point. Cyclin/cdk- phosphoylates proteins and initiates chromosome condensation, nuclear envelope disintegration. Destroys cyclin to stop itself. Increases other cyclins.

25. SIGNALING OF CELL CYCLE CONTROL ELEMENTS Internal signaling: M phase checkpoint- (correct spindle fiber attachment) kinetochore proteins-spindle+ spindle APCinactiveactive Cyclinsbreakdown kinetochore proteinsbreakdown holding sister chromatids together

26. External Signaling: G 1 checkpoint, Growth factors Ex. PDGF receptor cell cycle control

27. Fibroblast growth -Density-dependent inhibition -Anchorage dependence

28. Density-dependent inhibition of cell division

29. BIOLOGY OF CANCER Cancer is the loss of normal cell cycle regulation (a cell starts dividing out of control) 200 different kinds US: 10 million new cases/year1/3 people in their life time will develop some form of cancer Characteristics of Cancer Cells: Different appearance, De-differentiation (like stem cells) Loss of cell cycle control & contact inhibition, Heritable- daughter cells also cancerous Transplantablitity, Increased mutation rate Ability to spread (metastasis) & induce local blood vessel formation (angiogenesis) Breast cancer

30. BIOLOGY OF CANCER What can cause this? (7 th Ed. Ch. 19, pp 370-374) Genes that play a role in normal cell cycle control are altered in some way. 1. Genes that stimulate cell division Normal version of gene: Proto-oncogene -stimulate cell cycle Mutated version: Oncogene- actively promotes cancer. Activates cell division at inappropriate time or place Examples: myc- alters transcripton factor- (brain/blood, lung cancers) PDGF- alters GF or GF receptors (brain cancers) Ras- affects signal transduction (G protein) (lung, colon ovary, pancreas) Breast cancer

31. 2. Tumor Suppressor Genes: Two Classes - Genes involved in blocking cell division (checkpoints) Ex- p53- normally stops cell cycle when DNA is damaged and promotes apoptois if not fixed- found to be mutated in 50% of cancers RB- releases brake on cell cycle- eye, bone breast lung bladder cancers - DNA Repair Genes (fix mutations in DNA) ex: APC- DNA more replication errors (colon & Stomach cancers) hMH2 disrupts DNA mismatch repair (colon, uterus, ovarian cancers)

32. p21 (binds cdk) 0ncogene Tumor suppressor

34. p27 binds to cyclin and CDK blocking entry into S phase. Breast cancer prognosis is determined by p27 levels. Reduced levels of p27 predict a poor outcome for breast cancer patients.

35. To develop cancer it takes multiple mutations in the same cell. At least two mutations: One oncogene, one tumor suppressor gene.

36. Some people are predisposed to getting a particular type of cancer. (Genetic Pre-dispositions) Have ch. 5q mutation - hyperproliferation of epithelium, DNA hypomethylated-> Chromosome 12p (Ras gene)-> Ch 17p (p53 genes- Carcinoma-> more mutations-> metastasis

37. Metastasis- Cancer invasion 1.Cancer adheres to normal cells that lie next to tissue basement membrane (separates tissues) 2.Secretes substances that cause normal cell to move away 3.Secretes enzymes to penetrate basement membrane 4.Migrates through tissues- lymph

38. Cancer Treatment Strategies Surgery Chemotherapy Radiation Blocking hormone receptors Inducing differentiation Blocking telomerase activity Inhibiting angiogenesis Inducing apoptosis