1. THE CELL CYCLE IPMAT Regulation & Its Lifespan Implication

2. Why Do Cells Divide?

3. Reproduction Reproduction –Binary Fission in bacteria Tissue Growth Tissue Growth –Growth in multicellular organisms = more cells not larger cells Tissue Repair Tissue Repair Maintain High Surface Area:Volume Maintain High Surface Area:Volume –High volume = low efficiency

4. Parts in the Process: Chromosomes http://anatomy.iupui.edu/courses/histo_D502/D502f04/lecture.f04/cell.f04/cellf04.htmlhttp://mbbnet.umn.edu/icons/chromosome.jpeg

5. Parts in the Process: Centrioles & The MTOC http://sparkleberrysprings.com/v-web/b2/images/lotc/centriole14.jpg

6. Parts in the Process: Spindle Fibers & Kinetochores http://www.nikonsmallworld.com/gallery.php?grouping=year&year=2004&imagepos=18

7. Parts in the Process Centrioles Centrioles –animal cells only –MT – spindle fiber organization Centrosomes Centrosomes –plant & animal cells –AKA MTOC’s www.cellsalive.com http://osumolgen.siteturbine.com/sites/osumolgen/images/met3.jpg

8. Parts in the Process Chromosomes Chromosomes –Super-coiled DNA –centromeres Spindle Fibers Spindle Fibers –MT’s attached to centromeres @ kinetochore –Tracks for chromosome movement toward centrioles @ poles

9. http://www2.geneticsolutions.com/PageReq?id=3844:1873

12. The Cell Cycle I Interphase can be divided into 3 main substages: –G 1 –G 1 – Gap 1 - period of growth –S –S – Synthesis – DNA is copied (synthesized) –G 2 –G 2 – Gap 2 – preparation for division

13. The Cell Cycle The Cell Cycle (continued) G 2 I Following G 2 of Interphase, mitosis (M-phase) carries out division: –P –Prophase –M –Metaphase –A –Anaphase –T –Telophase & Cytokinesis http://www.biology.iupui.edu/biocourses/N100/2k4ch8mit osisnotes.html

14. Prophase Centrosomes to poles Nuclear membrane disappears Chromatin condenses to form chromosomes http://micro.magnet.fsu.edu/micro/gallery/mitosis/lateprophase.html http://www.dundee.ac.uk/biocentre/GRE%20Scientific%20images/pages/Prophase.htm

15. Metaphase Chromosomes in middle of cell Spindle fibers form Kinetochores attach to centromeres of each chromatid http://www.brown.edu/Courses/BI0020_Miller/images/metaphase-1.jpghttp://www.pc.vccs.edu/biology-labmanual/lab7mitmei/whitefishmeta.jpg

16. Anaphase Sister chromatids separate Chromatids move to poles using retreating spindle fibers (D.I.) http://micro.magnet.fsu.edu/micro/gallery/mitosis/earlyanaphase.htmlhttp://content.answers.com/main/content/wp/en/thumb/3/38/300px-Anaphase-flourescent.jpg

17. Telophase & Cytokinesis Telophase Telophase complete division of nucleus –Spindle fibers disappear –Nuclear membranes reappear Cytokinesis Cytokinesis complete division of cytoplasm –Cleavage furrow in animals –Cell plate in plants http://iknow.net/CDROMs/cell_cdrom/index.html Plant Animation Animal Mitosis

18. http://www.cbp.pitt.edu/faculty/yong_wan/index.html

19. Asymmetric Division Specialization of stem cells New daughter cells not identical http://labshelf.com/stem-cells-treatments-research.html

20. Regulation of Cell Cycle G 0 Checkpoints Apoptosis –Damage Prevention –Developmental Oncogenes –Mitosis accelerators Tumor Suppressor Genes –Mitosis brakes

21. G 0 – Exit From the Cell Cycle temporary (wbc’s) or permanent (nerve) Cancer cells do not ever enter G 0

22. Checkpoints in the Cell Cycle G 1 SMcyclins kinases G 1, S, and M occur when cyclins (proteins) bind & activate kinases. Kinases phosphorylate compounds necessary for division. G 1 SM kinases blocked if damage detected @ G 1, S, or M checkpoints.

23. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellCycle.html p53 ATM MAD

24. DNA Damage Detection G 1 G 1 –p53 –p53, a tumor suppressor, checks for damage before DNA replication –If damage cannot be repaired, p53 sends cell to to die so it cannot lead to cancer –P53 mutations implicated in > ½ of all human cancers S –ATM –ATM detects DNA damage, helps p53 send irreparably damaged cells to death, & maintains telomere length M –MAD –MAD stops mitosis if problems w/ microtubles in spindle fiber formation

26. Definition Mechanism of normal, controlled death by: –DNA fragmentation –Cytoplasm shrinkage –Membrane blebbing Cellular “suicide” No spillage or damage to nearby cells No inflammatory response http://www.sgul.ac.uk/depts/immunology/~dash/apoptosis/apoptosisvideo.ht ml

27. Is All Cell Death Equal? Necrosis –Messy cell death usually due to injury –Cellular “homicide” –Cell contents come spilling out leading to an inflammatory response. Swelling Redness Fever

29. Why Suicide? Development –Mouse paws (and human hands) use cell death to form digits.

31. Death As A Necessity For Life Immune system cells Virally infected cells Immune cells that don’t recognize “self” Removal of cytotoxic T cells after infection is conquered DNA damaged cells Sent to their death by p53 to prevent tumors

32. Disorders Involved Neurological disorders such as Huntington’s, Parkinson’s and Alzheimer’s diseases Too much apoptosis Cancer Not enough apoptosis Cell DivisionCell Death

33. Genes in Cancer Oncogenes Oncogenes –Genes known to speed up mitosis –Mitosis accelerators when ON (phosphorylation) –Cancer results if ON when should be OFF Tumor Suppressor Genes Tumor Suppressor Genes –Mitosis brakes –Tumors result if OFF when should be ON

34. Can a Cell Divide Forever? Normal CellsNO Normal Cells – NO –Telomeres –Telomeres, buffer zones @ tips of each chromosome, get shorter w/ each division –Cells die when telomeres gone EX: Aging effects are due to dead cells that can no longer be replaced

35. Can a Cell Divide Forever? Cancer CellsYES Cancer Cells – YES –Telomerase is ON Enzyme repairs telomeres after each division Embryonic Stem CellsYES Embryonic Stem Cells – YES –Fountain of Youth lies in harnessing anti- aging powers of telomerase w/o risk of cancer NO EASY TASK

36. www.hybridmedicalanimation.com http://www.ellisonfoundation.org/images/pfbs/p018_telomeres.jpg

37. The Cell Cycle http://bhs.smuhsd.org/bhsnew/academicprog/science/vaughn/Student%20Projects/Paul%20&%20Marcus/Cell_Replication.html