2. AP Biology 2008-2009 Regulation of Cell Division

3. AP Biology Coordination of cell division  A multicellular organism needs to coordinate cell division across different tissues & organs  critical for normal growth, development & maintenance

4. AP Biology G2G2 S G1G1 M metaphase prophase anaphase telophase interphase (G 1, S, G 2 phases) mitosis (M) cytokinesis (C) C  Frequency of cell division varies by cell type  embryo  skin cells  liver cells  mature nerve cells & muscle cells Frequency of cell division

5. AP Biology Overview of Cell Cycle Control  Two irreversible points in cell cycle  replication of genetic material  separation of sister chromatids  Checkpoints  process is assessed & possibly halted centromere sister chromatids single-stranded chromosomes double-stranded chromosomes There ’ s no turning back, now!

6. AP Biology Checkpoint control system  Checkpoints  cell cycle controlled by STOP & GO chemical signals at critical points  signals indicate if key cellular processes have been completed correctly

7. AP Biology Checkpoint control system  G 1 /S  can DNA synthesis begin?  G 2 /M  has DNA synthesis been completed correctly?  commitment to mitosis  spindle checkpoint  are all chromosomes attached to spindle?  can sister chromatids separate correctly?  3 major STOP & GO checkpoints:

8. AP Biology G 0 phase  G 0 phase  non-dividing, differentiated state  most human cells in G 0 phase  liver cells  in G 0, but can be “called back” to cell cycle by external cues  nerve & muscle cells  highly specialized  arrested in G 0 & can never divide

9. AP Biology  How do cells know when to divide?  cell communication signals  chemical signals in cytoplasm give cue  signals usually mean proteins  activators  inhibitors Activation of cell division experimental evidence: Can you explain this?

10.  Two types of regulatory proteins: cyclins and cyclin-dependent kinases (Cdks) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

11. Fig. 12-17a Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle Cyclin concentration MPF activity M M M SS G1G1 G1G1 G1G1 G2G2 G2G2

12. Fig. 12-17b Cyclin is degraded Cdk MPF Cdk M S G1G1 G 2 checkpoint Degraded cyclin Cyclin (b) Molecular mechanisms that help regulate the cell cycle G2G2 Cyclin accumulation

13.  An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase  Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

14. AP Biology Example of a Growth Factor  Platelet Derived Growth Factor (PDGF)  made by platelets in blood clots  binding of PDGF to cell receptors stimulates cell division in connective tissue  heal wounds Don’t forget to mention erythropoietin! (EPO)

15. Fig. 12-19 Anchorage dependence Density-dependent inhibition (a) Normal mammalian cells (b) Cancer cells 25 µm

16.  Cancer cells do not respond normally to the body’s control mechanisms  Cancer cells may not need growth factors to grow and divide: Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

17. AP Biology Development of Cancer  Cancer develops only after a cell experiences ~6 key mutations (“hits”)  unlimited growth  turn on growth promoter genes  ignore checkpoints  turn off tumor suppressor genes (p53)  escape apoptosis  turn off suicide genes  immortality = unlimited divisions  turn on chromosome maintenance genes  promotes blood vessel growth  turn on blood vessel growth genes  overcome anchor & density dependence  turn off touch-sensor gene It ’ s like an out-of-control car with many systems failing!

18. AP Biology What causes these “hits”?  Mutations in cells can be triggered by  UV radiation  chemical exposure  radiation exposure  heat  cigarette smoke  pollution  age  genetics

19. AP Biology Traditional treatments for cancers  Treatments target rapidly dividing cells  high-energy radiation  kills rapidly dividing cells  chemotherapy  stop DNA replication  stop mitosis & cytokinesis  stop blood vessel growth

20. AP Biology New “miracle drugs”  Drugs targeting proteins (enzymes) found only in cancer cells  Gleevec  treatment for adult leukemia (CML) & stomach cancer (GIST)  1st successful drug targeting only cancer cells Novartes without Gleevec with Gleevec

21.  Transformation  Tumor  Benign tumor  Malignant tumor  Metastasis Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

22. Fig. 12-20 Tumor A tumor grows from a single cancer cell. Glandular tissue Lymph vessel Blood vessel Metastatic tumor Cancer cell Cancer cells invade neigh- boring tissue. Cancer cells spread to other parts of the body. Cancer cells may survive and establish a new tumor in another part of the body. 1 2 3 4

23. Fig. 12-UN1 Telophase and Cytokinesis Anaphase Metaphase Prometaphase Prophase MITOTIC (M) PHASE Cytokinesis Mitosis S G1G1 G2G2

24. 1. Describe the structural organization of the prokaryotic genome and the eukaryotic genome 2. List the phases of the cell cycle; describe the sequence of events during each phase 3. List the phases of mitosis and describe the events characteristic of each phase 4. Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules, nonkinetochore microtubules, and asters Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

25. 5. Compare cytokinesis in animals and plants 6. Describe the process of binary fission in bacteria and explain how eukaryotic mitosis may have evolved from binary fission 7. Explain how the abnormal cell division of cancerous cells escapes normal cell cycle controls 8. Distinguish between benign, malignant, and metastatic tumors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

26. AP Biology 2008-2009 Any Questions??