1. Mitosis and Cancer PART 3 Honors Genetics Ms. Gaynor

2. Another Type of Cell Division: Binary Fission  Prokaryotes (bacteria) Reproduce by a type of cell division called binary fission

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. The cell cycle is HIGHLY regulated  The frequency of cell division Varies with the type of cell  These cell cycle differences Result from regulation at the molecular level http://highered.mcgraw- hill.com/sites/0072495855/student_view0/chapter2/animatio n__how_the_cell_cycle_works.html http://highered.mcgraw- hill.com/sites/0072495855/student_view0/chapter2/animatio n__how_the_cell_cycle_works.html

5. Cell Cycle Checkpoints  The clock has specific checkpoints a critical control point where stop and “go-ahead” signals can regulate cycle These signals report whether crucial cellular processes up to that specific point have been completed and completed correctly  There are 3 checkpoints G1 checkpoint G2 Checkpoint M checkpoint  spindle assembly checkpoint

6. The Cell Cycle Control System  The sequential events of the cell cycle Are directed by a distinct cell cycle control system, which is similar to a clock Figure 12.14 Control system G 2 checkpoint M checkpoint G 1 checkpoint G1G1 S G2G2 M

7. G1 Checkpoint 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

8. G1 Checkpoint  Restriction point just before entry into S phase  Checks cell size & original DNA for damage  Makes key decisions  should cell divide or delay division and enter G0 (resting) phase  Most cells stop at this stage and enter a resting state called G 0

9. G2 Checkpoint  Checks cell size  Triggers start of M phase  DNA is frequently damaged prior to mitosis  if this happens, the cell cycle is arrested via inactivation of cell cycle “control” proteins

10. M Checkpoint  Makes sure spindle assembly is correct  Makes sure all chromosomes are aligned at the mitotic plate

12. The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases  Two types of regulatory proteins in cytoplasm are involved in cell cycle control Cyclins Cyclin-dependent kinases (Cdks)

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

14. 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

15. cyclin degrades & breaks apart

16. 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

17. Important Cyclins and CDKs Cyclin D-CDK4 Cyclin E-CDK2 Cyclin A-CDK2 Cyclin B-CDC2

18. Control of Cell Cycle Animations  http://highered.mcgraw- hill.com/sites/0072495855/student_vie w0/chapter2/animation__control_of_th e_cell_cycle.html http://highered.mcgraw- hill.com/sites/0072495855/student_vie w0/chapter2/animation__control_of_th e_cell_cycle.html  Amination #8 Amination #8 http://www.cellsalive.com/apop.htm

19. Programmed Cell Death (Apoptosis)  In apoptosis  http://www.biooncology.com/bioonc/research/apoptosis/ind ex.m http://www.biooncology.com/bioonc/research/apoptosis/ind ex.m  Cell signaling is involved in programmed cell death  needed to maintain healthy tissues/ cell function 2 µm Figure 21.17

20. Stop and Go Signs: Internal and External Signals at the Checkpoints  Both internal (inside the cell) and external (outside the cell) signals Control the cell cycle checkpoints

21. Internal and External Signals  Internal signals DNA synthesis Growth/Nutrition CDK/Cyclins  External signals Growth factors & Hormones Density Dependent Inhibition Anchorage Dependence

22. Influences on Cell Division  Growth factors & hormones Stimulate other cells to divide  In density-dependent inhibition Crowded cells stop dividing  Most animal cells exhibit anchorage dependence In which they must be attached to a structure to divide  Ex: extracellular matrix of a tissue

23. 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

24. Cancer cells Exhibit neither density-dependent inhibition nor 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

25. Loss of Cell Cycle Controls in Cancer Cells  Cancer cells Do not respond normally to the body’s control mechanisms Form tumors  TUMOR = mass or group of abnormal dividing cells

26. Why?  Don’t need growth factors  maybe they make their own growth factors  Mutations in GENES!!! Ex: cyclin or Cdk genes

27. Loss of Cell Cycle Controls in Cancer Cells  Cancer cells transformation Normal cell  cancer cells using process of transformation 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!!!

28. Malignant tumors  These tumors invade surrounding tissues and can metastasize Exporting cancer cells to other parts of the body where they may form secondary tumors USE BLOOD STREAM and LYMPH VESSELS TO SPREAD!!! USE BLOOD STREAM and LYMPH VESSELS TO SPREAD!!! http://www.hhmi.org/biointeractive/media/angiogene sis-lg.mov http://www.hhmi.org/biointeractive/media/angiogene sis-lg.mov

29. 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

30. 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 

31. Cancer Causing Agents 1. Genetics (inherited) 2. Spontaneous mutation 3. Envinromental Mutagens (a.k.a- carcinogen) Sun Viruses Chemicals

32. Cancer Animations- REVIEW Cancer Movie  http://www.cancerquest.org/index.c fm?page=3102&lang=english http://www.cancerquest.org/index.c fm?page=3102&lang=english  http://science.education.nih.gov/su pplements/nih1/cancer/activities/ac tivity2_animations.htm http://science.education.nih.gov/su pplements/nih1/cancer/activities/ac tivity2_animations.htm

33. Flashcard Vocabulary  http://highered.mcgraw- hill.com/sites/0078757150/student_ view0/vocabulary_eflashcards.html http://highered.mcgraw- hill.com/sites/0078757150/student_ view0/vocabulary_eflashcards.html