1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint TextEdit Art Slides for Biology, Seventh Edition Neil Campbell and Jane Reece Chapter 12 The Cell Cycle

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.1 Chromosomes in a dividing cell

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.2 The functions of cell division 20 µm 100 µm 200 µm (a) Reproduction. An amoeba, a single-celled eukaryote, is dividing into two cells. Each new cell will be an individual organism (LM). (b) Growth and development. This micrograph shows a sand dollar embryo shortly after the fertilized egg divided, forming two cells (LM). (c) Tissue renewal. These dividing bone marrow cells (arrow) will give rise to new blood cells (LM).

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.3 Eukaryotic chromosomes 50 µm

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.4 Chromosome duplication and distribution during cell division 0.5 µm Chromosome duplication (including DNA synthesis) Centromere Separation of sister chromatids Sister chromatids Centrometers Sister chromatids A eukaryotic cell has multiple chromosomes, one of which is represented here. Before duplication, each chromosome has a single DNA molecule. Once duplicated, a chromosome consists of two sister chromatids connected at the centromere. Each chromatid contains a copy of the DNA molecule. Mechanical processes separate the sister chromatids into two chromosomes and distribute them to two daughter cells.

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.5 The cell cycle INTERPHASE G1G1 S (DNA synthesis) G2G2 Cytokinesis Mitosis MITOTIC (M) PHASE

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.6 Exploring The Mitotic Division of an Animal Cell G 2 OF INTERPHASEPROPHASE PROMETAPHASE Centrosomes (with centriole pairs) Chromatin (duplicated) Early mitotic spindle Aster Centromere Fragments of nuclear envelope Kinetochore Nucleolus Nuclear envelope Plasma membrane Chromosome, consisting of two sister chromatids Kinetochore microtubule Nonkinetochore microtubules

8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G 2 of Interphase A nuclear envelope bounds the nucleus. The nucleus contains one or more nucleoli (singular, nucleolus). Two centrosomes have formed by replication of a single centrosome. In animal cells, each centrosome features two centrioles. Chromosomes, duplicated during S phase, cannot be seen individually because they have not yet condensed. The light micrographs show dividing lung cells from a newt, which has 22 chromosomes in its somatic cells (chromosomes appear blue, microtubules green, intermediate filaments red). For simplicity, the drawings show only four chromosomes. Prophase The chromatin fibers become more tightly coiled, condensing into discrete chromosomes observable with a light microscope. The nucleoli disappear. Each duplicated chromosome appears as two identical sister chromatids joined together. The mitotic spindle begins to form. It is composed of the centrosomes and the microtubules that extend from them. The radial arrays of shorter microtubules that extend from the centrosomes are called asters (“stars”). The centrosomes move away from each other, apparently propelled by the lengthening microtubules between them. Prometaphase The nuclear envelope fragments. The microtubules of the spindle can now invade the nuclear area and interact with the chromosomes, which have become even more condensed. Microtubules extend from each centrosome toward the middle of the cell. Each of the two chromatids of a chromosome now has a kinetochore, a specialized protein structure located at the centromere. Some of the microtubules attach to the kinetochores, becoming “kinetochore microtubules.” These kinetochore microtubules jerk the chromosomes back and forth. Nonkinetochore microtubules interact with those from the opposite pole of the spindle.

9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings METAPHASEANAPHASETELOPHASE AND CYTOKINESIS Spindle Metaphase plate Nucleolus forming Cleavage furrow Nuclear envelope forming Centrosome at one spindle pole Daughter chromosomes

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Metaphase Metaphase is the longest stage of mitosis, lasting about 20 minutes. The centrosomes are now at opposite ends of the cell. The chromosomes convene on the metaphase plate, an imaginary plane that is equidistant between the spindle’s two poles. The chromosomes’ centromeres lie on the metaphase plate. For each chromosome, the kinetochores of the sister chromatids are attached to kinetochore microtubules coming from opposite poles. The entire apparatus of microtubules is called the spindle because of its shape. Anaphase Anaphase is the shortest stage of mitosis, lasting only a few minutes. Anaphase begins when the two sister chromatids of each pair suddenly part. Each chromatid thus becomes a full- fledged chromosome. The two liberated chromosomes begin moving toward opposite ends of the cell, as their kinetochore microtubules shorten. Because these microtubules are attached at the centromere region, the chromosomes move centromere first (at about 1 µm/min). The cell elongates as the nonkinetochore microtubules lengthen. By the end of anaphase, the two ends of the cell have equivalent—and complete—collections of chromosomes. Telophase Two daughter nuclei begin to form in the cell. Nuclear envelopes arise from the fragments of the parent cell’s nuclear envelope and other portions of the endomembrane system. The chromosomes become less condensed. Mitosis, the division of one nucleus into two genetically identical nuclei, is now complete. Cytokinesis The division of the cytoplasm is usually well underway by late telophase, so the two daughter cells appear shortly after the end of mitosis. In animal cells, cytokinesis involves the formation of a cleavage furrow, which pinches the cell in two.

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.7 The mitotic spindle at metaphase Sister chromatids Metaphase Plate Kinetochores Overlapping nonkinetochore microtubules Kinetochores microtubules Centrosome Chromosomes Microtubules 0.5 µm Centrosome Aster 1 µm

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.8 Inquiry During anaphase, do kinetochore microtubules shorten at their spindle pole ends or their kinetochore ends? EXPERIMENT 1 The microtubules of a cell in early anaphase were labeled with a fluorescent dye that glows in the microscope (yellow). Spindle pole Kinetochore

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2 A Laser was used to mark the kinetochore mircotubles by eliminating the fluorescnce in a region between one spindle pole and the chromosomes. As anaphase proceeded, researches monitored the changes in the lengths of the microtubles on either side of the mark. Mark RESULTS As the chromosomes moved toward the poles, the microtubule segments on the kinetochore side of the laser mark shortened, while those on the spindle pole side stayed the same length.

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings CONCLUSION This experiment demonstrated that during anaphase, kinetochore microtubules shorten at their kinetochore ends, not at their spindle pole ends. This is just one of the experiments supporting the hypothesis that during anaphase, a chromosome tracks along a microtubule as the microtubule depolymerizes at its kinetochore end, releasing tubulin subunits Chromosome movement Microtubule Motor protein Chromosome Kinetochore Tubulin subunits

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.9 Cytokinesis in animal and plant cells Daughter cells Cleavage furrow Contractile ring of microfilaments Daughter cells 100 µm 1 µm Vesicles forming cell plate Wall of patent cell Cell plate New cell wall (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (SEM)

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.10 Mitosis in a plant cell 1 Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is staring to from. Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelop will fragment. Metaphase. The spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate. Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of cell as their kinetochore microtubles shorten. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divided the cytoplasm in two, is growing toward the perimeter of the parent cell. 23 4 5 Nucleus Nucleolus Chromosome Chromatine condensing

17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.11 Bacterial cell division (binary fission) 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

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.12 A hypothetical sequence for the evolution of mitosis Most eukaryotes. In most other eukaryotes, including plants and animals, the spindle forms outside the nucleus, and the nuclear envelope breaks down during mitosis. Microtubules separate the chromosomes, and the nuclear envelope then re-forms. Dinoflagellates. In unicellular protists called dinoflagellates, the nuclear envelope remains intact during cell division, and the chromosomes attach to the nuclear envelope. Microtubules pass through the nucleus inside cytoplasmic tunnels, reinforcing the spatial orientation of the nucleus, which then divides in a fission process reminiscent of bacterial division. Diatoms. In another group of unicellular protists, the diatoms, the nuclear envelope also remains intact during cell division. But in these organisms, the microtubules form a spindle within the nucleus. Microtubules separate the chromosomes, and the nucleus splits into two daughter nuclei. Prokaryotes. During binary fission, the origins of the daughter chromosomes move to opposite ends of the cell. The mechanism is not fully understood, but proteins may anchor the daughter chromosomes to specific sites on the plasma membrane. (a) (b) (c) (d) Bacterial chromosome Microtubules Intact nuclear envelope Chromosomes Kinetochore microtubules Intact nuclear envelope Kinetochore microtubules Fragments of nuclear envelope Centrosome

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.13 Inquiry Are there molecular signals in the cytoplasm that regulate the cell cycle? In each experiment, cultured mammalian cells at two different phases of the cell cycle were induced to fuse. EXPERIMENTS RESULTS CONCLUSION The results of fusing cells at two different phases of the cell cycle suggest that molecules present in the cytoplasm of cells in the S or M phase control the progression of phases. When a cell in the S phase was fused with a cell in G 1, the G 1 cell immediately entered the S phase—DNA was synthesized. When a cell in the M phase was fused with a cell in G 1, the G 1 cell immediately began mitosis— a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. S SSMM MG1G1 G1G1 Experiment 1 Experiment 2

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.14 Mechanical analogy for the cell cycle control system Control system G 2 checkpoint M checkpoint G 1 checkpoint G1G1 S G2G2 M

21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.15 The G 1 checkpoint G 1 checkpoint G1G1 G1G1 G0G0 (a) If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. (b) If a cell does not receive a go-ahead signal at the G 1 checkpoint, the cell exits the cell cycle and goes into G 0, a nondividing state.

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.16 Molecular control of the cell cycle at the G 2 checkpoint Accumulated cyclin molecules combine with recycled Cdk mol- ecules, producing enough molecules of MPF to pass the G 2 checkpoint and initiate the events of mitosis. MPF promotes mitosis by phosphorylating various proteins. MPF‘s activity peaks during metaphase. 3 During G 1, conditions in the cell favor degradation of cyclin, and the Cdk component of MPF is recycled. 5 During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G 1 phase. 4 2 Synthesis of cyclin begins in late S phase and continues through G 2. Because cyclin is protected from degradation during this stage, it accumulates. 1 Cdk G 2 checkpoint Cyclin MPF Cyclin is degraded Degraded Cyclin G1G1 G2G2 S M G1G1 G1G1 S G2G2 G2G2 S M M MPF activity Cyclin Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle (b) Molecular mechanisms that help regulate the cell cycle Relative Concentration

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.17 Inquiry Does platelet-derived growth factor (PDGF) stimulate the division of human fibroblast cells in culture? EXPERIMENT A sample of connective tissue was cut up into small pieces. Enzymes were used to digest the extracellular matrix, resulting in a suspension of free fibroblast cells. Cells were transferred to sterile culture vessels containing a basic growth medium consisting of glucose, amino acids, salts, and antibiotics (as a precaution against bacterial growth). PDGF was added to half the vessels. The culture vessels were incubated at 37°C. 3 2 1 Petri plate Without PDGF With PDGF Scalpels

24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In a basic growth medium without PDGF (the control), cells failed to divide. In a basic growth medium plus PDGF, cells proliferated. The SEM shows cultured fibroblasts. Without PDGF With PDGF RESULTS This experiment confirmed that PDGF stimulates the division of human fibroblast cells in culture. CONCLUSION a b 10 µm

25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.18 Density-dependent inhibition and anchorage dependence of cell division 25 µm 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). Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. 25 µm Cancer cells. Cancer cells usually continue to divide well beyond a single layer, forming a clump of overlapping cells. Normal mammalian cells. The availability of nutrients, growth factors, and a substratum for attachment limits cell density to a single layer. (a) (b)

26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.19 The growth and metastasis of a malignant breast tumor A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue. Cancer cells spread through lymph and blood vessels to other parts of the body. A small percentage of cancer cells may survive and establish a new tumor in another part of the body. 2 43 1 Tumor Glandular tissue Cancer cell Blood vessel Lymph vessel Metastatic Tumor

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Unnumbered Figure p. 235

28. Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings 1.Using the data in the table below, the best conclusion concerning the difference between the S phases for beta and gamma is that a.gamma contains more DNA than beta. b.beta and gamma contain the same amount of DNA. c.beta contains more RNA than gamma. d.gamma contains 48 times more DNA and RNA than beta. e.beta is a plant cell and gamma is an animal cell. Cell TypeG1G1 SG2G2 M Beta18241216 Delta100000 Gamma18481420 Minutes Spent in Cell Cycle Phases

29. Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings 2.Cytokinesis usually, but not always, follows mitosis. If a cell completed mitosis but not cytokinesis, what would be the result? a.a cell with a single large nucleus b.a cell with high concentrations of actin and myosin c.a cell with two abnormally small nuclei d.a cell with two nuclei e.a cell with two nuclei but with half the amount of DNA

30. Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings 3.Taxol is an anticancer drug extracted from the Pacific yew tree. In animal cells, taxol disrupts microtubule formation by binding to microtubules and accelerating their assembly from the protein precursor, tubulin. Surprisingly, this stops mitosis. Specifically, taxol must affect a.the fibers of the mitotic spindle. b.anaphase. c.formation of the centrioles. d.chromatid assembly. e.the S phase of the cell cycle.

31. Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings 4.Movement of the chromosomes during anaphase would be most affected by a drug that a.reduced cyclin concentrations. b.increased cyclin concentrations. c.prevented elongation of microtubules. d.prevented shortening of microtubules. e.prevented attachment of the microtubules to the kinetochore.

32. Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings 5.Measurements of the amount of DNA per nucleus were taken on a large number of cells from a growing fungus. The measured DNA levels ranged from 3 to 6 picograms per nucleus. In which stage of the cell cycle was the nucleus with 6 picograms of DNA? a.G 0 b.G 1 c.S d.G 2 e.M

33. Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings 6.A group of cells is assayed for DNA content immediately following mitosis and is found to have an average of 8 picograms of DNA per nucleus. Those cells would have __________ picograms at the end of the S phase and __________ picograms at the end of G 2. a.8... 8 b.8... 16 c.16... 8 d.16... 16 e.12... 16

34. Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings 7.A particular cell has half as much DNA as some of the other cells in a mitotically active tissue. The cell in question is most likely in a.G 1. b.G 2. c.prophase. d.metaphase. e.anaphase.

35. Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings 8.In some organisms, mitosis occurs without cytokinesis occurring. This will result in a.cells with more than one nucleus. b.cells that are unusually small. c.cells lacking nuclei. d.destruction of chromosomes. e.cell cycles lacking an S phase.

36. Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings 10.The rhythmic changes in cyclin concentration in a cell cycle are due to a.its increased production once the restriction point is passed. b.the cascade of increased production once its enzyme is phosphorylated by MPF. c.its degradation, which is initiated by active MPF. d.the correlation of its production with the production of Cdk. e.the binding of the growth factor PDGF.

37. Copyright © 2004 Pearson Education, Inc. publishing as Benjamin Cummings 11.A cell in which of the following phases would have the least amount of DNA? a.G 0 b.G 2 c.prophase d.metaphase e.anaphase