Cell Division and its Importance in Reproduction and Growth

1. Chapter 12 The Cell Cycle

2. Overview: The Key Roles of Cell Division • The ability of organisms to reproduce best distinguishes living things from nonliving matter • The continuity of life is based upon the reproduction of cells, or cell division

4. In unicellular organisms, division of one cell reproduces the entire organism • Multicellular organisms depend on cell division for: • Development from a fertilized cell • Growth • Repair • Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division

5. LE 12-2 Sand dollar embryo after fertilized egg divided Dividing bone marrow cells give rise to new blood cells Amoeba-single celled eukaryote 100 µm 200 µm 20 µm Reproduction Growth and development Tissue renewal

6. Concept 12.1: Cell division results in genetically identical daughter cells • Cells duplicate their genetic material before they divide, ensuring that each daughter cell receives an exact copy of the genetic material, DNA • A dividing cell duplicates its DNA, allocates the two copies to opposite ends of the cell, and only then splits into daughter cells

7. Cellular Organization of the Genetic Material • A cell’s endowment of DNA (its genetic information) is called its genome -Typical human cell is about 2 m of DNA– 250,000 times greater than the cell’s diameter • DNA molecules in a cell are packaged into chromosomes (Gr chroma, color and soma, body)

8. Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus • Somatic (nonreproductive) cells have two sets of chromosomes -Humans 46 c’somes made up two 23 sets • Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells • Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division

9. LE 12-3 25 µm

10. Distribution of Chromosomes During Cell Division • In preparation for cell division, DNA is replicated and the chromosomes condense • Each duplicated chromosome has two sister chromatids, which separate during Anaphase of cell division -Cohesions: adhesive protein complexes attached along the lengths of the sister chromatids • The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached

11. LE 12-4 0.5 µm 1. Before duplication each c’some has a single DNA mc Chromosome duplication (including DNA synthesis) 2. Once replicated c’some consists of 2 chromatids. Each chromatid containing a copy of DNA Centromere Sister chromatids Separation of sister chromatids 3. Separation of the 2 chromatids into c’some and into two daughter cells Centromeres Sister chromatids

12. Eukaryotic cell division consists of: • Mitosis, the division of the nucleus • Cytokinesis, the division of the cytoplasm • Gametes are produced by a variation of cell division called meiosis • Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell

13. Concept 12.2: The mitotic phase alternates with interphase in the cell cycle • In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis • To Flemming, it appeared that the cell simply grew larger between one cell division and the next • Now we know that many critical events occur during this stage in a cell’s life

14. Phases of the Cell Cycle • The cell cycle consists of • Mitotic (M) phase (mitosis and cytokinesis) • Interphase (cell growth and copying of chromosomes in preparation for cell division) • Interphase (about 90% of the cell cycle) can be divided into subphases: • G1 phase (“first gap”) • S phase (“synthesis”) • G2 phase (“second gap”)

15. LE 12-5 90% of the cycle Grows & copies c’some INTERPHASE C’somes duplicated S (DNA synthesis) G1 Cell Grows Mitosis Cytokinesis G2 Continues to grow and prepares for M-phase MITOTIC (M) PHASE

16. Mitosis is conventionally divided into five phases: • Prophase • Prometaphase • Metaphase • Anaphase • Telophase • Cytokinesis is well underway by late telophase [Animations and videos listed on slide following figure]

17. LE 12-6ca G2 OF INTERPHASE PROPHASE PROMETAPHASE

18. LE 12-6da 10 µm TELOPHASE AND CYTOKINESIS METAPHASE ANAPHASE

19. Video: Animal Mitosis Video: Sea Urchin (time lapse) Animation: Mitosis (All Phases) Animation: Mitosis Overview Animation: Late Interphase Animation: Prophase Animation: Prometaphase Animation: Metaphase Animation: Anaphase Animation: Telophase

20. The Mitotic Spindle: A Closer Look • The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis • Assembly of spindle microtubules begins in the centrosome, the microtubule organizing center • The centrosome replicates, forming two centrosomes that migrate to opposite ends of the cell, as spindle microtubules grow out from them -G2 phase • An aster (a radial array of short microtubules) extends from each centrosome -Prophase

21. The spindle includes the centrosomes, the spindle microtubules, and the asters • Some spindle microtubules attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate

22. LE 12-7 Aster Centrosome Sister chromatids Metaphase plate Chromosomes Microtubules Kineto- chores Overlapping nonkinetochore microtubules Kinetochore microtubules Centrosome 1 µm 0.5 µm

23. In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell • The microtubules shorten by depolymerizing at their kinetochore ends

24. LE 12-8b As c’some move poleward, c’some are walked along a MT as the MT depolymerizes at its kinetochore end, releasing tubulin subunits. Chromosome movement Kinetochore Tubulin subunits Motor protein Microtubule Chromosome Pg 235 Figure 12.8 Borisy’s lab at University of Wisconsin 1987

25. Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell • In telophase, genetically identical daughter nuclei form at opposite ends of the cell

26. Cytokinesis: A Closer Look • In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow • In plant cells, a cell plate forms during cytokinesis Animation: Cytokinesis

27. LE 12-9a Contractile ring: composed of actin & myosin filaments (pulling of drawstring) 100 µm Cleavage furrow Cleavage furrow deepens until cell is pinched off producing two id cells Daughter cells Contractile ring of microfilaments Cleavage of an animal cell (SEM)

28. LE 12-9b Vesicles derived from Golgi Apparatus move along MT  middle of cell coalescecell plate Vesicles forming cell plate Wall of parent cell 1 µm Cell plate enlarges until it fuses with plasma membrane 2 new daughter cells New cell wall Cell plate Daughter cells Cell plate formation in a plant cell (TEM)

29. LE 12-10 Chromatin condensing Nucleus 10 µm Chromosomes Cell plate Nucleolus Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelope will fragment. Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is starting to form. Metaphase. The spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divide the cytoplasm in two, is growing toward the perimeter of the parent cell. Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of the cell as their kinetochore micro- tubules shorten.

30. Binary Fission • Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission (division in half) • In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart

31. LE 12-11_1 Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Two copies of origin

32. LE12-11_2 Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Two copies of origin Origin Origin Replication continues. One copy of the origin is now at each end of the cell.

33. LE 12-11_3 Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Two copies of origin Origin Origin Replication continues. One copy of the origin is now at each end of the cell. Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. Two daughter cells result.

34. The Evolution of Mitosis • Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission • Certain protists exhibit types of cell division that seem intermediate between binary fission and mitosis

35. LE 12-12 Bacterial chromosome Prokaryotes Chromosomes Microtubules Intact nuclear envelope Dinoflagellates Kinetochore microtubules Intact nuclear envelope Diatoms Kinetochore microtubules Centrosome Fragments of nuclear envelope Most eukaryotes

36. Concept 12.3: The cell cycle is regulated by a molecular control system • The frequency of cell division varies with the type of cell -liver cells maintain the ability to divide but will when appropriate (damage) -nerve and muscle cells do not divide in mature humans • These cell cycle differences result from regulation at the molecular level

37. Evidence for Cytoplasmic Signals • The cell cycle appears to be driven by specific chemical signals present in the cytoplasm • Some evidence for this hypothesis comes from experiments in which cultured mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei

38. LE 12-13 Experiment 1 Experiment 2 Cell cycle is driven by specific molecular signals present in the cytoplasm M S G1 G1 M S M S When a cell in the M phase was fused with a cell in G1, the G1 cell immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. When a cell in the S phase was fused with a cell in G1, the G1 cell immediately entered the S phase—DNA was synthesized.

39. 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 -triggers and coordinates key events in the cell cycle • The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received -signals are transmitted within the cell by _? __

40. Restriction Point LE 12-14 G1 checkpoint Control system S G1 G2 M System is subject to regulation at various checkpoints (3) M checkpoint G2 checkpoint

41. For many cells, the G1 checkpoint seems to be the most important one • If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide • If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase -most of the human body cells are in G0 phase -external clues such as GF released during injuiry can call back cells from the G0 phase

42. LE 12-15 G0 G1 checkpoint G1 G1 If a cell does not receive a go-ahead signal at the G1 checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state. If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

43. The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases • Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks) -remember from Ch 11 the role of protein kinases? -Cyclins (proteins): cycling fluctuating concentrating in the cell -Cdks; the activity rises and falls with changes in the concentration of its cyclin partner • The activity of cyclins and Cdks fluctuates during the cell cycle

44. LE12-16a MPF triggers the cell’s passage from G2 into M-phase G1 S G2 G1 M M M S G2 MPF activity Cyclin Relative concentration Time Fluctuation of MPF activity and cyclin concentration during the cell cycle

45. LE12-16b 1. Synthesis of cyclin begins in late S phase G2 5. Conditions favor degradation of cyclin & Cdk component of MPF is recycled G1 Cyclin S Cdk M Degraded cyclin G2 accumulation G2 checkpoint Cdk 4. During anaphase, cyclin of MPF is degraded, terminating the M-phase Cyclin is degraded 2. Accumled cyclin and Cdk mc’s produce MPF to pass G2 mitosis Cyclin MPF 3. MPF promotes M-phase by phsphryltng proteins

46. Stop and Go Signs: Internal and External Signals at the Checkpoints • 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 • For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture

47. LE 12-17 Scalpels Petri plate Without PDGF With PDGF Without PDGF With PDGF 10 mm

48. Another example of external signals is density-dependent inhibition, in which crowded cells stop dividing • Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide

49. LE 12-18a 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). 25 µm Normal mammalian cells

50. Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence