1. Cell Cycle Regulation and Cancer Lecture #20 Honors Biology Ms. Day

2. Another Type of Cell Division: Binary Fission  Prokaryotes (bacteria) Reproduce by a type of cell division called binary fission No nucleus  no karyokinesis!!

3.  In binary fission,  The bacterial chromosome replicates  The two daughter chromosomes move apart Origin of replication E. coli cell Bacterial Chromosome Cell wall Plasma Membrane Two copies of origin Origin Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. 1 Replication continues. One copy of the origin is now at each end of the cell. 2 Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. 3 Two daughter cells result.4 Figure 12.11

4. Cell Cycle needs to be controlled (Regulated)  The cell cycle has 3 checkpoints A place where stop and go signals can regulate (control) cycle Signals report if things up to that specific point have: been completed and completed correctly  There are 3 checkpoints G1 checkpoint G2 Checkpoint M checkpoint

5. The Cell Cycle Control System Figure 12.14 Control system G 2 checkpoint M checkpoint G 1 checkpoint G1G1 S G2G2 M

6. Checkpoint = give “go” or “stop” signals G 1 checkpoint G1G1 G1G1 G0G0 If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in cell cycle. If a cell does not receive a go-ahead signal at the G 1 checkpoint, cell exits the cell cycle and goes into G 0, a nondividing state. Figure 12.15 A, B

7. http://highered.mcgraw- hill.com/sites/0072495855/student_view0/chapter2/animation__control_of_the_cell_cycle.html Chromosomes are lined up in the middle properly of replicated DNA of unreplicated (original) DNA

8. What controls the checkpoints?  Two types of proteins in cytoplasm Cyclins cyclin-dependent kinases (Cdks)

9. INACTIVE FORM CYCLIN DEPENDENT KINASE (CDK) CDK/CYCLIN COMPLEX CYCLIN + ACTIVE FORM

10. Active vs. Inactive??  What happens when cyclins and cdks are in the ACTIVE form? Cells can pass through the cell cycle to the NEXT phase  What happens when cyclins and cdks are in the INACTIVE form? Cells can NOT pass through the cell cycle to the NEXT phase

11. cyclin degrades & breaks apart

12. What degrades (breaks down) cyclins?  Proteolytic enzymes (proteins) Break down/degrade cyclins  cause them to fluctuate in [ ] “PROTEO” means protein “LYTIC” means break or lyse REMEMBER: Cyclin concentration fluctuates (changes) Cdk concentration stays the SAME

13. Programmed Cell Death (Apoptosis)  If cell doesn’t “pass” checkpoint, it goes through apoptosis  http://www.dnatube.com/video/1188/Ap optosis-animation http://www.dnatube.com/video/1188/Ap optosis-animation  Cell signaling is involved in programmed cell death  needed to maintain healthy tissues/ cell function 2 µm Figure 21.17 http://bio- alive.com/categories/ apoptosis/apoptosis.h tm

14. What other things control cell division?  Both internal and external signals control the cell cycle/cell division…  Internal signals CDK/Cyclins at checkpoints  External signals Growth factors Density dependent inhibition Anchorage dependence

15. External (outside the cell) Influences on Cell Division  Growth factors Stimulate other cells to divide  In density-dependent inhibition Crowded cells stop dividing  Most animal cells exhibit anchorage dependence Cells must be attached to a structure to divide  Ex: protein of a tissue or another cell

16. Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). Normal mammalian cells. **The availability of nutrients, growth factors, and a substratum for attachment limits cell density to a single layer. (a) 25 µm Figure 12.18 A

17. Cancer cells Do NOT follow the “rules”  No checkpoints and no density-dependent inhibition or anchorage dependence Immortal cells (if enough nutrients) 25 µm Cancer cells usually continue to divide well beyond a single layer, forming a clump of overlapping cells. Figure 12.18 B

18. Loss of Cell Cycle Controls in Cancer Cells  Cancer cells form tumors  TUMOR = mass or group of abnormal dividing cells

19. Types of Tumors  Cancer cells form tumors  Benign  “fine” Clump of cells remain at orginal spot “cancer”  Malignant  “ m ean”  “cancer” Loose/destroy attachments to other cells  they can spread or move (called metastasize)!!!

20. Why?  Don’t need growth factors  maybe they make their own growth factors  Mutations in GENES that make proteins involved in control systems!!! Cancer Movie  http://www.hhmi.org/biointeractive/using-p53-fight-cancer http://www.hhmi.org/biointeractive/using-p53-fight-cancer  http://www.cancerquest.org/index.cfm?page=3102&lang=english http://www.cancerquest.org/index.cfm?page=3102&lang=english

21. Cancer cells are “hungry”…  Angiogenesis is the recruitment of blood vessels from the network of neighbouring vessels.  Without blood and the nutrients it carries, a tumor would be unable to continue growing. http://www.hhmi.org/biointeractive/angiogenesis

22. Cancer Treatment  Radiation  destroys DNA in cancer cells (these cells have lost ability to repair damage)  Chemotherapeutic drugs interfere with specific steps in cell cycle Also effects normal cells  Also effects normal cells 

23. Tumor Glandular tissue Cancer cell Blood vessel Lymph vessel Metastatic Tumor Cancer cells invade neighboring tissue. 2 A small percentage of cancer cells may survive and establish a new tumor in another part of the body. 4 Cancer cells spread through lymph and blood vessels to other parts of the body. 3 A tumor grows from a single cancer cell. 1 Figure 12.19

24. Angiogenesis (the formation of new blood vessels) and Metatasis  http://www.hhmi.org/biointeractive /media/angiogenesis-lg.mov http://www.hhmi.org/biointeractive /media/angiogenesis-lg.mov  http://www.hhmi.org/biointeractive /media/vegf-lg.mov http://www.hhmi.org/biointeractive /media/vegf-lg.mov