Unit III : Cell Cycle

1. Unit III : Cell Cycle A: Mitosis and Cytokinesis B: Meiosis and Gamete Formation

2. Rudolf Virchow • A German Physician • 1855 : “Where a cell exists, there must have been a preexisting cell, just as the animal arises from an animal and the plant only from a plant.” • “Omnis cellula e cellula”

3. Format of Cell Growth • Cell Growth • Increase in the number of cells • Increase in the size of cells • Volume – Surface Area Relationship • Volume increases as the cube of the radius • Surface area increases as the square of the radius • Problems with transport – wastes out of cell and nutrients into cell

4. The Nucleus Controls Metabolic Functions • Chromosomes (DNA) contain genetic information for all aspects of cell structures and functions • Must produce EXACT copy of nucleus (chromosomes) for each new cell

5. Definitions • Cell cycle : The life of a cell from its origin in the division of a parent cell until its own division into two • Genome : The total DNA of a cell • Chromosomes : Packages of DNA molecules • Somatic Cells : All body cells except the reproductive cells (46) • Gametes : Reproductive cells (23)

6. More Definitions • Chromatin : DNA-Protein complex within the nucleus • Sister Chromatids : Identical duplicated chromosomes • Centromere : The centralized region joining two sister chromatids

7. Mitosis or Karyokinesis • Duplication and division of nucleus and its contents (chromosomes) • Need exact copies of cells with complete set of genetic information

8. Chromosome Duplication

9. A: Interphase • Accounts for 90% of Cell Cycle • Metabolically active – growth and synthesis • Typical Eukaryotic appearance • Chromosomes present but not visible • Chromatin – long thin thread like appearance of the DNA + protein in an uncoiled nature • Animal cells have 2 pairs of centrioles outside of the nuclear region • Interphase : Divided into three sub-phases • G1, S, and G2

10. A: Interphase G1 • First “Gap” • Cell is growing • S • Chromosomes duplicated • G2 • Second “Gap” • Cell grows more in anticipation of cell division

11. Chromosomes of Interphase : DNA plus protein core • Chromatin : thin thread like appearance • DNA is metabolically active as cell functions and grows = G1 • Synthesis of new DNA = exact copies of each chromosome • 46 chromosomes = G1 • 92 chromosomes = S (synthesis of DNA) • S = this cell is preparing to divide …….how do you know cell has completed S if chromatin isn’t visible? • Weigh cell X ng vs. 2X ng

12. G2 – Second Growth (Gap) • This specific growth is directed towards cell division • Different from G1 • Proteins for spindle fibers, etc

13. B: Prophase • Nuclear membrane fragments and incorporated into ER • Chromatin/Chromosomes start to coli – shorten – thicken – more visible • Visible as duplicated pair • Formed during S phase of interphase joined together by centromere

14. B: Prophase • Animal Cell has 2 pairs of centrioles at start of prophase • Begin to separate to opposite ends or poles of cell • Organize protein from cytoplasm into spindle fibers ad prophase continues • Works in 360 degree fashion • Animal cells have Astral rays radiating from each pair of centrioles • Plant cell = protein polymerization to form spindle fibers

15. Progression of Chromosomes

16. B: Prophase • Top = Prophase with chromosomes & spindle fibers becoming visible • Bottom = Late prophase or prometaphase as chromosomes condense and nuclear membrane fragments

17. Lets Review

18. Prophase Animation

19. C: Metaphase • Books/movies discuss prometaphase = late prophase or early metaphase • Shortest phase • No nuclear membrane visible • Chromatid pairs maximally shortened and visible • Chromatic pairs have attached to spindle fibers via a centromere and migrated towards middle/center of cell • Called metaphase plate or equatorial plate

20. Centromeres and Kintechores • Kinetochore = proteins plus DNA at centromeres • One per chromatid/replicated chromosome • Spindle fibers from one pole attach to each kinetochore • Non-kinetochore microtubules for the spindle fibers

21. Colchicine • A drug that inhibits the synthesis of microtubules • Spindle fibers do not form • Stops mitosis • Cells do not progress out of metaphase • Never enters anaphase

22. C: Metaphase

23. D: Anaphase • Separation of identical chromatids which move towards opposite poles • Centromere (DNA) quickly separate as proteins holding identical chromatids • Kintechores of each chromatid start moving towards opposite poles as microtubules depolymerize at centromere • The two poles of the cell now contain equivalent and complete collections of chromosomes

24. D: Anaphase • Experiment demonstrating the migration of chromosomes to each pole of the cell • Centromere side stayed same length, Kinetochore side shortened • MIGRATION!

25. D: Anaphase

26. E: Telophase • Reversal of prophase • Nuclear membrane reforms • Chromosomes uncoil, become thinner and longer • Nucleoli may reappear • Spindle fibers break down • A multinucleated cell results

27. E: Telophase

28. E: Telophase

29. Cytokinesis : Duplication and division of cytoplasm and its contents • Animal Cell – cleavage furrow forms at site of metaphase plate as microfilaments pull membrane inwards to produce two independent daughter cells • Plant Cell – vesicles derived from golgi move along microtubules and collect in center of cell, spanning the cell, with contents of cell plate forming new cell wall (middle lamella) – cell membrane invagination follows

30. Lets Review

31. Cytokinesis

32. Mitosis in a Plant Cell

33. Origin of Mitosis ? • Prokaryotes  Bacteria • Must divide to grow and proliferate • Called binary fission • The origin of Mitosis? • A similar process

34. Figure 12.10 Bacterial cell division (binary fission)

35. Figure 12.10 Bacterial cell division (binary fission)

36. Figure 12.10 Bacterial cell division (binary fission) (Layer 3)

37. Figure 12.11 A hypothesis for the evolution of mitosis

38. Figure 12.12 Evidence for cytoplasmic chemical signals in cell cycle regulation

39. Cell Cycle Regulation • Checkpoint – stop and go-ahead signals can regulate the cycle • Animal cells will typically stop at check points unless being overridden by go-ahead signals • Three Major checkpoints : G1, G2, M phases • G1 Checkpoint –most important • If the cell passes G1 it will typically complete the cycle and divide • G0 phase – a Non-dividing state • Most cells of the human body are in this state

40. Figure 12.13 Mitotic Regulation

41. Cyclins and Cyclin – Dependent Kinases • Kinases : enzymes that activate or inactivate other proteins by phosphorylation • Not active unless attached to a cyclin • Cyclin – a protein that cyclically fluctuates within the cell • Kinases are called : cyclin-dependent kinases (CDKs) • MFK – promotes mitosis by phosphorylating various proteins • Maturation-promoting-factor • Discovered first

42. Figure 12.14 Molecular control of the cell cycle at the G2 checkpoint

43. Figure 12.15 The effect of a growth factor on cell division - Fibroblasts

44. *Cells typically grow in a density dependent manner *Cells are anchorage dependent - they must attach to a container wall or ECM *This is the normal state *Cancer cells do not exhibit a density or anchorage dependence -they have escaped cell cycle controls! Figure 12.16 Density-dependent inhibition of cell division

45. Cancer Cells • Escape cell cycle controls • No anchorage or density dependence • Can divide in culture infinitely • Most cells divide 20-50 times and die • Cancer cells = “Immortal”

46. Cancer Cells • A normal cell undergoes “transformation” • If it survives the immune system it can proliferate into a tumor • A mass of abnormal cells within a normal tissue • Benign • Cells remain at the original site • Malignant • Becomes invasive enough to effect other organs

47. Figure 12.17 The growth and metastasis of a malignant breast tumor

48. END MITOSIS