BIOLOGY. The Cell Cycle CAMPBELL. Reece Urry Cain Wasserman Minorsky Jackson. Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick

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1 CAMPBELL BIOLOGY TENTH EDITION Reece Urry Cain Wasserman Minorsky Jackson 12 The Cell Cycle Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick

2 The Key Roles of Cell Division The ability of organisms to produce more of their own kind best distinguishes living things from nonliving matter The continuity of life is based on the reproduction of cells, or cell division

3 Figure 12.1

4 Figure 12.1a Chromosomes (blue) are moved by cell machinery (red) during division of a rat kangaroo cell.

5 Video: Sea Urchin Embryonic Development (time-lapse)

6 In unicellular organisms, division of one cell reproduces the entire organism Multicellular eukaryotes 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

7 Figure μm 50 μm (a) Reproduction (b) Growth and development 20 µm (c) Tissue renewal

8 Figure 12.2a 100 μm (a) Reproduction

9 Figure 12.2b 50 μm (b) Growth and development

10 Figure 12.2c 20 μm (c) Tissue renewal

11 Concept 12.1: Most cell division results in genetically identical daughter cells Most cell division results in daughter cells with identical genetic information, DNA The exception is meiosis, a special type of division that can produce sperm and egg cells

12 Cellular Organization of the Genetic Material All the DNA in a cell constitutes the cell s genome A genome can consist of a single DNA molecule (common in prokaryotic cells) or a number of DNA molecules (common in eukaryotic cells) DNA molecules in a cell are packaged into chromosomes

13 Figure μm

14 Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus Somatic cells (nonreproductive cells) have two sets of chromosomes Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells

15 Distribution of Chromosomes During Eukaryotic Cell Division In preparation for cell division, DNA is replicated and the chromosomes condense Each duplicated chromosome has two sister chromatids (joined copies of the original chromosome), attached along their lengths by cohesins The centromere is the narrow waist of the duplicated chromosome, where the two chromatids are most closely attached

16 Figure 12.4 Sister chromatids Centromere 0.5 μm

17 During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei Once separate, the chromatids are called chromosomes

18 Figure Chromosomes Centromere Chromosomal DNA molecules Chromosome arm

19 Figure Chromosomes Centromere Chromosomal DNA molecules 2 Chromosome arm Chromosome duplication Sister chromatids

20 Figure Chromosomes Centromere Chromosomal DNA molecules 2 Chromosome arm Chromosome duplication 3 Sister chromatids Separation of sister chromatids

21 Eukaryotic cell division consists of Mitosis, the division of the genetic material in 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 half as many chromosomes as the parent cell

22 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

23 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)

24 Interphase (about 90% of the cell cycle) can be divided into subphases G 1 phase ( first gap ) S phase ( synthesis ) G 2 phase ( second gap ) The cell grows during all three phases, but chromosomes are duplicated only during the S phase

25 Figure 12.6 G 1 S (DNA synthesis) G 2

26 Figure 12.7a 10 μm G 2 of Interphase Centrosomes (with centriole pairs) Chromosomes (duplicated, uncondensed) Early mitotic spindle Prophase Aster Centromere Fragments of nuclear envelope Prometaphase Nonkinetochore microtubules Nucleolus Nuclear envelope Plasma membrane Two sister chromatids of one chromosome Kinetochore Kinetochore microtubule

27 Figure 12.7b 10 μm Metaphase Anaphase Telophase and Cytokinesis Metaphase plate Cleavage furrow Nucleolus forming Spindle Centrosome at one spindle pole Daughter chromosomes Nuclear envelope forming

28 Figure 12.7c G 2 of Interphase Prophase Centrosomes (with centriole pairs) Centrosomes (duplicated, uncondensed) Early mitotic spindle Aster Centromere Nucleolus Nuclear envelope Plasma membrane Two sister chromatids of one chromosome

29 Figure 12.7d Prometaphase Metaphase Fragments of nuclear envelope Nonkinetochore microtubules Metaphase plate Kinetochore Kinetochore microtubule Spindle Centrosome at one spindle pole

30 Video: Microtubules in Cell Division

31 Figure 12.7e Anaphase Telophase and Cytokinesis Cleavage furrow Nucleolus forming Daughter chromosomes Nuclear envelope forming

32 Video: Microtubules in Anaphase

33 Figure 12.7f 10 μm G 2 of Interphase

34 Video: Nuclear Envelope Formation

35 Figure 12.7g 10 µm Prophase

36 Figure 12.7h 10 µm Prometaphase

37 Figure 12.7i 10 µm Metaphase

38 Figure 12.7j 10 µm Anaphase

39 Figure 12.7k 10 µm Telophase and Cytokinesis

40 BioFlix: Mitosis

41 Video: Animal Mitosis (time-lapse)

42 The Mitotic Spindle: A Closer Look The mitotic spindle is a structure made of microtubules that controls chromosome movement during mitosis In animal cells, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center The centrosome replicates during interphase, forming two centrosomes that migrate to opposite ends of the cell during prophase and prometaphase

43 An aster (a radial array of short microtubules) extends from each centrosome The spindle includes the centrosomes, the spindle microtubules, and the asters

44 During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes Kinetochores are protein complexes associated with centromeres At metaphase, the chromosomes are all lined up at the metaphase plate, a plane midway between the spindle s two poles

45 Figure 12.8 Sister chromatids Aster Centrosome Metaphase plate (imaginary) Kinetochores Microtubules Overlapping nonkinetochore microtubules Chromosomes Kinetochore microtubules Centrosome 1 µm 0.5 µm

46 Figure 12.8a Microtubules Chromosomes Centrosome 1 µm

47 Figure 12.8b Kinetochores Kinetochore microtubules 0.5 µm

48 Video: Spindle Formation During Mitosis

49 In anaphase the cohesins are cleaved by an enzyme called separase Sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell The microtubules shorten by depolymerizing at their kinetochore ends

50 Figure 12.9 Experiment Kinetochore Results Spindle pole Mark Conclusion Chromosome movement Motor Microtubule protein Chromosome Kinetochore Tubulin subunits

51 Figure 12.9a Experiment Kinetochore Spindle pole Mark

52 Figure 12.9b Results Conclusion Chromosome movement Motor Microtubule protein Chromosome Kinetochore Tubulin subunits

53 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 Cytokinesis begins during anaphase or telophase and the spindle eventually disassembles

54 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

55 Figure (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM) Cleavage furrow 100 µm Vesicles forming cell plate Wall of parent cell 1 µm Cell plate New cell wall Contractile ring of microfilaments Daughter cells Daughter cells

56 Figure 12.10a (a) Cleavage of an animal cell (SEM) Cleavage furrow 100 µm Contractile ring of microfilaments Daughter cells

57 Figure 12.10aa Cleavage furrow 100 µm

58 Figure 12.10b (b) Cell plate formation in a plant cell (TEM) Vesicles forming cell plate Wall of parent cell 1 µm Cell plate New cell wall Daughter cells

59 Figure 12.10ba Vesicles forming cell plate Wall of parent cell 1 µm

60 Animation: Cytokinesis

61 Video: Myosin and Cytokinesis

62 10 µm Figure Nucleus Nucleolus Chromosomes condensing Chromosomes 1 Prophase 2 Prometaphase Cell plate 3 Metaphase 4 Anaphase 5 Telophase

63 Figure 12.11a Nucleus Nucleolus Chromosomes condensing 1 Prophase 10 µm

64 Figure 12.11b Chromosomes 2 10 µm Prometaphase

65 Figure 12.11c 3 Metaphase 10 µm

66 Figure 12.11d 4 Anaphase 10 µm

67 Figure 12.11e Cell plate 5 Telophase 10 µm

68 Binary Fission in Bacteria Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart The plasma membrane pinches inward, dividing the cell into two

69 Figure Chromosome replication begins. Origin of replication Two copies of origin E. coli cell Cell wall Plasma membrane Bacterial chromosome

70 Figure Chromosome replication begins. Origin of replication Two copies of origin E. coli cell Cell wall Plasma membrane Bacterial chromosome 2 One copy of the origin is now at each end of the Origin Origin cell.

71 Figure Chromosome replication begins. Origin of replication Two copies of origin E. coli cell Cell wall Plasma membrane Bacterial chromosome 2 One copy of the origin is now at each end of the cell. Origin Origin 3 Replication finishes.

72 Figure Chromosome replication begins. Origin of replication Two copies of origin E. coli cell Cell wall Plasma membrane Bacterial chromosome 2 One copy of the origin is now at each end of the cell. Origin Origin 3 Replication finishes. 4 Two daughter cells result.

73 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

74 Figure (a) Bacteria Bacterial chromosome (c) Diatoms and some yeasts Kinetochore microtubule Intact nuclear envelope Chromosomes Microtubules Kinetochore microtubule (b) Dinoflagellates Intact nuclear envelope (d) Most eukaryotes Fragments of nuclear envelope

75 Concept 12.3: The eukaryotic cell cycle is regulated by a molecular control system The frequency of cell division varies with the type of cell These differences result from regulation at the molecular level Cancer cells manage to escape the usual controls on the cell cycle

76 The Cell Cycle Control System 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

77 Figure Experiment Experiment 1 Experiment 2 S G 1 M G 1 Results S S M M G 1 nucleus immediately entered S phase and DNA was synthesized. G 1 nucleus began mitosis without chromosome duplication. Conclusion Molecules present in the cytoplasm control the progression to S and M phases.

78 The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock The cell cycle control system is regulated by both internal and external controls The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received

79 Figure G 1 checkpoint G 1 Control system S M G 2 M checkpoint G 2 checkpoint

80 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) The activity of a Cdk rises and falls with changes in concentration of its cyclin partner MPF (maturation-promoting factor) is a cyclin-cdk complex that triggers a cell s passage past the G 2 checkpoint into the M phase

81 Figure M G 1 S G 2 M G 1 S G 2 M G 1 MPF activity Cyclin concentration Degraded cyclin Cdk Cdk Time Cyclin is degraded MPF Cyclin G 2 checkpoint (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle (b) Molecular mechanisms that help regulate the cell cycle

82 Figure 12.16a M G 1 S M G 1 S M G 1 G 2 G 2 MPF activity Cyclin concentration Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle

83 Figure 12.16b Cdk Degraded cyclin Cdk Cyclin is degraded MPF G 2 checkpoint Cyclin (b) Molecular mechanisms that help regulate the cell cycle

84 Stop and Go Signs: Internal and External Signals at the Checkpoints Many signals registered at checkpoints come from cellular surveillance mechanisms within the cell Checkpoints also register signals from outside the cell Three important checkpoints are those in G 1, G 2, and M phases

85 For many cells, the G 1 checkpoint seems to be the most important If a cell receives a go-ahead signal at the G 1 checkpoint, it will usually complete the S, G 2, 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 G 0 phase

86 Figure G 1 checkpoint G 0 G 1 Without go-ahead signal, cell enters G 0. G 1 With go-ahead signal, cell continues cell cycle. G 1 S (a) G 1 checkpoint M G 2 G 1 G 1 M G 2 M G 2 M checkpoint Prometaphase Anaphase G 2 checkpoint Metaphase Without full chromosome attachment, stop signal is received. With full chromosome attachment, go-ahead signal is received. (b) M checkpoint

87 Figure 12.17a G 1 checkpoint G 0 G 1 Without go-ahead signal, cell enters G 0. (a) G 1 checkpoint G 1 With go-ahead signal, cell continues cell cycle.

88 Figure 12.17b G 1 G 1 M G 2 M G 2 M checkpoint Prometaphase Anaphase G 2 checkpoint Metaphase Without full chromosome attachment, stop signal is received. With full chromosome attachment, go-ahead signal is received. (b) M checkpoint

89 An example of an internal signal is that cells will not begin anaphase until all chromosomes are properly attached to the spindle at the metaphase plate This mechanism assures that daughter cells have the correct number of chromosomes

90 External factors that influence cell division include specific growth factors Growth factors are released by certain cells and stimulate other cells to divide Platelet-derived growth factor (PDGF) is made by blood cell fragments called platelets In density-dependent inhibition, crowded cells will stop dividing

91 Figure A sample of human connective tissue is cut up into small pieces. Petri dish Scalpels

92 Figure A sample of human connective tissue is cut up into small pieces. Petri dish Scalpels 2 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts.

93 Figure A sample of human connective tissue is cut up into small pieces. Petri dish Scalpels 2 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. 3 Cells are transferred to culture vessels. 4 PDGF is added to half the vessels.

94 10 µm Figure A sample of human connective tissue is cut up into small pieces. Petri dish Scalpels 2 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. 3 Cells are transferred to culture vessels. 4 PDGF is added to half the vessels. Without PDGF With PDGF Cultured fibroblasts (SEM)

95 Figure 12.18a 10 µm Cultured fibroblasts (SEM)

96 Most cells also exhibit anchorage dependence to divide, they must be attached to a substratum Density-dependent inhibition and anchorage dependence check the growth of cells at an optimal density Cancer cells exhibit neither type of regulation of their division

97 Figure Anchorage dependence: cells require a surface for division Density-dependent inhibition: cells form a single layer Density-dependent inhibition: cells divide to fill a gap and then stop 20 µm 20 µm (a) Normal mammalian cells (b) Cancer cells

98 Figure 12.19a 20 µm (a) Normal mammalian cells

99 Figure 12.19b 20 µm (b) Cancer cells

100 Loss of Cell Cycle Controls in Cancer Cells Cancer cells do not respond normally to the body s control mechanisms Cancer cells may not need growth factors to grow and divide They may make their own growth factor They may convey a growth factor s signal without the presence of the growth factor They may have an abnormal cell cycle control system

101 A normal cell is converted to a cancerous cell by a process called transformation Cancer cells that are not eliminated by the immune system form tumors, masses of abnormal cells within otherwise normal tissue If abnormal cells remain only at the original site, the lump is called a benign tumor

102 Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors Localized tumors may be treated with high-energy radiation, which damages the DNA in the cancer cells To treat metastatic cancers, chemotherapies that target the cell cycle may be used

103 Figure µm Breast cancer cell (colorized SEM) Tumor Lymph vessel Blood vessel Metastatic tumor Glandular tissue Cancer cell 1 A tumor grows 2 Cancer cells invade 3 from a single neighboring tissue. cancer cell. Cancer cells spread through lymph and blood vessels to other parts of the body. 4 A small percentage of cancer cells may metastasize to another part of the body.

104 Figure 12.20a Tumor Glandular tissue 1 A tumor grows 2 Cancer cells invade 3 from a single neighboring tissue. cancer cell. Cancer cells spread through lymph and blood vessels to other parts of the body.

105 Figure 12.20b Lymph vessel Metastatic tumor Blood vessel Cancer cell 3 Cancer cells spread through lymph and blood vessels to other parts of the body. 4 A small percentage of cancer cells may metastasize to another part of the body.

106 Figure 12.20c 5 µm Breast cancer cell (colorized SEM)

107 Recent advances in understanding the cell cycle and cell cycle signaling have led to advances in cancer treatment Coupled with the ability to sequence the DNA of cells in a particular tumor, treatments are becoming more personalized

108 Figure 12.UN01a Number of cells 200 Control A B C Treated A B C Amount of fluorescence per cell (fluorescence units)

109 Figure 12.UN01b

110 Figure 12.UN02 G 1 S Cytokinesis Mitosis G 2 MITOTIC (M) PHASE Prophase Telophase and Cytokinesis Anaphase Metaphase Prometaphase

111 Figure 12.UN03

112 Figure 12.UN04

2014 Pearson Education, Inc.

2014 Pearson Education, Inc. 2 The Cell Cycle CAMPBELL BIOLOGY TENTH EDITION Reece Urry Cain Wasserman Minorsky Jackson The Key Roles of Cell Division The ability of organisms to produce more of their own kind best distinguishes living

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