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Chapter 12 The Cell Cycle
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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 on the reproduction of cells, or cell division. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Figure 12.1 How do a cell’s chromosomes change during cell division?
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Multicellular organisms depend on cell division for:
In unicellular organisms, division of one cell reproduces the entire organism. Multicellular organisms depend on cell division for: Development from a fertilized cell Growth and development Repair (tissue renewal) Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Figure 12.2 The functions of cell division
100 µm 200 µm 20 µm (a) Reproduction (b) Growth and development (c) Tissue renewal Figure 12.2 The functions of cell division
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100 µm (a) Reproduction Figure 12.2 The functions of cell division
Fig. 12-2a Figure 12.2 The functions of cell division 100 µm Figure 12.2 The functions of cell division (a) Reproduction
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Figure 12.2 The functions of cell division
Fig. 12-2b Figure 12.2 The functions of cell division 200 µm Figure 12.2 The functions of cell division (b) Growth and development
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20 µm (c) Tissue renewal Fig. 12-2c
Figure 12.2 The functions of cell division (c) Tissue renewal
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Concept 12.1: Cell division results in genetically identical daughter cells
Most cell division results in daughter cells with identical genetic information, DNA (mitosis or binary fission). A special type of division (meiosis) produces nonidentical daughter cells. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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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. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Fig. 12-3 Figure 12.3 Eukaryotic chromosomes 20 µm
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Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus.
Somatic cells (nonreproductive cells) have two sets of chromosomes; diploid cells, 2n. Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells; one set of chromosomes; haploid cells,n. Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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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, which separate during cell division. The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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0.5 µm Chromosomes DNA molecules Chromo- some arm Chromosome
Fig. 12-4 0.5 µm Chromosomes DNA molecules Chromo- some arm Chromosome duplication (including DNA synthesis) Centromere Sister chromatids Figure 12.4 Chromosome duplication and distribution during cell division Separation of sister chromatids Centromere Sister chromatids
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Eukaryotic cell division consists of:
Mitosis- division of the nucleus Cytokinesis- 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. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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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. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Phases of the Cell Cycle
The cell cycle consists of: Mitotic (M) phase - mitosis and cytokinesis Interphase -cell growth and copying of chromosomes in prep for cell division Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Interphase (about 90% of the cell cycle) can be divided into subphases:
G1 phase (“first gap”) S phase (“synthesis”) G2 phase (“second gap”) The cell grows during all three phases, but chromosomes are duplicated only during the S phase. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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S (DNA synthesis) G1 Cytokinesis G2 Mitosis
Fig. 12-5 INTERPHASE S (DNA synthesis) G1 Cytokinesis G2 Mitosis Figure 12.5 The cell cycle MITOTIC (M) PHASE
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Mitosis is conventionally divided into five phases:
Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis is well underway by late telophase For the Cell Biology Video Myosin and Cytokinesis, go to Animation and Video Files. BioFlix: Mitosis Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Chromosome, consisting of two sister chromatids
Fig. 12-6 G2 of Interphase Prophase Prometaphase Metaphase Anaphase Telophase and Cytokinesis Centrosomes (with centriole pairs) Chromatin (duplicated) Early mitotic spindle Aster Centromere Fragments of nuclear envelope Nonkinetochore microtubules Metaphase plate Cleavage furrow Nucleolus forming Figure 12.6 The mitotic division of an animal cell Daughter chromosomes Nucleolus Nuclear envelope Plasma membrane Chromosome, consisting of two sister chromatids Kinetochore Kinetochore microtubule Spindle Centrosome at one spindle pole Nuclear envelope forming
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G2 of Interphase Prophase Prometaphase
Fig. 12-6a Figure 12.6 The mitotic division of an animal cell G2 of Interphase Prophase Prometaphase
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Chromosome, consisting of two sister chromatids
Fig. 12-6b G2 of Interphase Prophase Prometaphase Centrosomes (with centriole pairs) Chromatin (duplicated) Early mitotic spindle Aster Centromere Fragments of nuclear envelope Nonkinetochore microtubules Figure 12.6 The mitotic division of an animal cell Nucleolus Nuclear envelope Plasma membrane Chromosome, consisting of two sister chromatids Kinetochore Kinetochore microtubule
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Telophase and Cytokinesis
Fig. 12-6c Figure 12.6 The mitotic division of an animal cell Metaphase Anaphase Telophase and Cytokinesis
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Telophase and Cytokinesis
Fig. 12-6d Metaphase Anaphase Telophase and Cytokinesis Metaphase plate Cleavage furrow Nucleolus forming Figure 12.6 The mitotic division of an animal cell Daughter chromosomes Nuclear envelope forming Spindle Centrosome at one spindle pole
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The Mitotic Spindle: A Closer Look
The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis. Prophase- assembly of spindle microtubules begins in the centrosome (aka: microtubule organizing center). Centrosome replicates, forming two centrosomes that migrate to opposite ends of the cell, as spindle microtubules grow out from them. For the Cell Biology Video Spindle Formation During Mitosis, go to Animation and Video Files. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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An aster (a radial array of short microtubules) extends from each centrosome.
The spindle includes the centrosomes, the spindle microtubules, and the asters. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes. At metaphase, the chromosomes are all lined up at the metaphase plate (midway point between the spindle’s two poles). Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Microtubules Chromosomes
Fig. 12-7 Aster Centrosome Sister chromatids Microtubules Chromosomes Metaphase plate Kineto- chores Centrosome 1 µm Figure 12.7 The mitotic spindle at metaphase Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 µm
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The microtubules shorten by depolymerizing at their kinetochore ends.
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. For the Cell Biology Video Microtubules in Anaphase, go to Animation and Video Files. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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EXPERIMENT RESULTS CONCLUSION Kinetochore Spindle pole Mark Chromosome
Fig. 12-8 EXPERIMENT Kinetochore Spindle pole Mark RESULTS Figure 12.8 At which end do kinetochore microtubules shorten during anaphase? CONCLUSION Chromosome movement Kinetochore Motor protein Tubulin subunits Microtubule Chromosome
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EXPERIMENT Kinetochore Spindle pole Mark RESULTS Fig. 12-8a
Figure 12.8 At which end do kinetochore microtubules shorten during anaphase? RESULTS
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Chromosome movement Kinetochore Tubulin Motor Subunits Microtubule
Fig. 12-8b CONCLUSION Chromosome movement Kinetochore Tubulin Subunits Motor protein Microtubule Figure 12.8 At which end do kinetochore microtubules shorten during anaphase? Chromosome
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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. For the Cell Biology Video Microtubules in Cell Division, go to Animation and Video Files. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Video: Sea Urchin (Time Lapse)
Video: Animal Mitosis Video: Sea Urchin (Time Lapse) For the Cell Biology Video Nuclear Envelope Formation, go to Animation and Video Files. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Fig. 12-9 Figure 12.9 Cytokinesis in animal and plant cells Vesicles
forming cell plate Wall of parent cell 1 µm 100 µm Cleavage furrow Cell plate New cell wall Figure 12.9 Cytokinesis in animal and plant cells Contractile ring of microfilaments Daughter cells Daughter cells (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM)
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(a) Cleavage of an animal cell (SEM)
Fig. 12-9a 100 µm Cleavage furrow Figure 12.9a Cytokinesis in animal and plant cells Contractile ring of microfilaments Daughter cells (a) Cleavage of an animal cell (SEM)
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(b) Cell plate formation in a plant cell (TEM)
Fig. 12-9b Vesicles forming cell plate Wall of parent cell 1 µm Cell plate New cell wall Figure 12.9b Cytokinesis in animal and plant cells Daughter cells (b) Cell plate formation in a plant cell (TEM)
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10 µm Fig. 12-10 Nucleus Chromatin condensing Nucleolus Chromosomes
Cell plate Figure Mitosis in a plant cell 1 Prophase 2 Prometaphase 3 Metaphase 4 Anaphase 5 Telophase
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Nucleus 1 Prophase Chromatin condensing Nucleolus Fig. 12-10a
Figure Mitosis in a plant cell 1 Prophase
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Chromosomes 2 Prometaphase Fig. 12-10b
Figure Mitosis in a plant cell 2 Prometaphase
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Fig c Figure Mitosis in a plant cell 3 Metaphase
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Fig d Figure Mitosis in a plant cell 4 Anaphase
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10 µm Cell plate 5 Telophase Fig. 12-10e
Figure Mitosis in a plant cell 5 Telophase
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Binary Fission 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. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Cell wall Origin of replication Plasma membrane E. coli cell Bacterial
Fig Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Two copies of origin Figure Bacterial cell division by binary fission
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Cell wall Origin of replication Plasma membrane E. coli cell Bacterial
Fig Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Two copies of origin Origin Origin Figure Bacterial cell division by binary fission
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Cell wall Origin of replication Plasma membrane E. coli cell Bacterial
Fig Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Two copies of origin Origin Origin Figure Bacterial cell division by binary fission
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Cell wall Origin of replication Plasma membrane E. coli cell Bacterial
Fig Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Two copies of origin Origin Origin Figure Bacterial cell division by binary fission
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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. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Fig. 12-12 Bacterial chromosome (a) Bacteria Chromosomes Microtubules
Intact nuclear envelope (b) Dinoflagellates Kinetochore microtubule Intact nuclear envelope Figure A hypothetical sequence for the evolution of mitosis (c) Diatoms and yeasts Kinetochore microtubule Fragments of nuclear envelope (d) Most eukaryotes
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Bacterial chromosome (a) Bacteria Chromosomes Microtubules
Fig ab Bacterial chromosome (a) Bacteria Chromosomes Microtubules Figure A hypothetical sequence for the evolution of mitosis Intact nuclear envelope (b) Dinoflagellates
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Kinetochore microtubule Intact nuclear envelope (c) Diatoms and yeasts
Fig cd Kinetochore microtubule Intact nuclear envelope (c) Diatoms and yeasts Kinetochore microtubule Figure A hypothetical sequence for the evolution of mitosis Fragments of nuclear envelope (d) Most eukaryotes
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The frequency of cell division varies with the type of cell.
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 cell cycle differences result from regulation at the molecular level. 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. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Fig EXPERIMENT Experiment 1 Experiment 2 Figure Do molecular signals in the cytoplasm regulate the cell cycle? S G1 M G1 RESULTS S S M M When a cell in the S phase was fused with a cell in G1, the G1 nucleus immediately entered the S phase—DNA was synthesized. When a cell in the M phase was fused with a cell in G1, the G1 nucleus immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. Figure Do molecular signals in the cytoplasm regulate the cell cycle?
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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. Cell cycle control system -regulated by both internal and external controls. Clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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G1 checkpoint Control system S G1 G2 M M checkpoint G2 checkpoint
Fig G1 checkpoint Control system S G1 G2 M Figure Mechanical analogy for the cell cycle control system M checkpoint G2 checkpoint
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For many cells, the G1 checkpoint seems to be the most important one.
If 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. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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G0 G1 G1 G1 checkpoint (b) Cell does not receive a go-ahead signal
Fig G0 G1 checkpoint Figure The G1 checkpoint G1 G1 Cell receives a go-ahead signal (b) Cell does not receive a go-ahead signal
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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 cyclins and Cdks fluctuates during the cell cycle. MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G2 checkpoint into the M phase. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Fig RESULTS 5 30 4 20 3 % of dividing cells (– ) Protein kinase activity (– ) 2 10 1 Figure How does the activity of a protein kinase essential for mitosis vary during the cell cycle? 100 200 300 400 500 Time (min) Figure How does the activity of a protein kinase essential for mitosis vary during the cell cycle?
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Figure 12.17 Molecular control of the cell cycle at the G2 checkpoint
S G2 M G1 S G2 M G1 MPF activity Cyclin concentration Figure Molecular control of the cell cycle at the G2 checkpoint Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle G1 S Cdk Figure Molecular control of the cell cycle at the G2 checkpoint Cyclin accumulation M Degraded cyclin G2 G2 Cdk Cyclin is degraded checkpoint Cyclin MPF (b) Molecular mechanisms that help regulate the cell cycle
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(a) Fluctuation of MPF activity and cyclin concentration during
Fig a Figure Molecular control of the cell cycle at the G2 checkpoint M G1 S G2 M G1 S G2 M G1 MPF activity Cyclin concentration Figure Molecular control of the cell cycle at the G2 checkpoint Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle
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(b) Molecular mechanisms that help regulate the cell cycle
Fig b G1 S Cdk Cyclin accumulation M Degraded cyclin G2 G2 checkpoint Cdk Figure Molecular control of the cell cycle at the G2 checkpoint Cyclin is degraded Cyclin MPF (b) Molecular mechanisms that help regulate the cell cycle
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Stop and Go Signs: Internal and External Signals at the Checkpoints
A. An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase. B. Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide. C. For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Figure 12.18 The effect of a growth factor on cell division
Scalpels Petri plate Without PDGF cells fail to divide Figure The effect of a growth factor on cell division With PDGF cells prolifer- ate Cultured fibroblasts 10 µm
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D. Another example of external signals is density-dependent inhibition, in which crowded cells stop dividing. E. Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Density-dependent inhibition
Fig Figure Density-dependent inhibition and anchorage dependence of cell division Anchorage dependence Density-dependent inhibition Density-dependent inhibition Figure Density-dependent inhibition and anchorage dependence of cell division 25 µm 25 µm (a) Normal mammalian cells (b) Cancer cells
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Cancer cells: exhibit neither density-dependent inhibition nor anchorage dependence.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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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. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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A normal cell is converted to a cancerous cell by a process called transformation.
Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue. If abnormal cells remain at the original site, the lump is called a benign tumor. Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form secondary tumors. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Figure 12.20 The growth and metastasis of a malignant breast tumor
Lymph vessel Tumor Blood vessel Cancer cell Glandular tissue Metastatic tumor 1 A tumor grows from a single cancer cell. 2 Cancer cells invade neigh- boring tissue. 3 Cancer cells spread to other parts of the body. 4 Cancer cells may survive and establish a new tumor in another part of the body. Figure The growth and metastasis of a malignant breast tumor
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G1 S Cytokinesis Mitosis G2 MITOTIC (M) PHASE Prophase Telophase and
Fig. 12-UN1 INTERPHASE G1 S Cytokinesis Mitosis G2 MITOTIC (M) PHASE Prophase Telophase and Cytokinesis Prometaphase Anaphase Metaphase
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Fig. 12-UN2
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Fig. 12-UN3
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Fig. 12-UN4
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Fig. 12-UN5
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Fig. 12-UN6
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You should now be able to:
Describe the structural organization of the prokaryotic genome and the eukaryotic genome. List the phases of the cell cycle; describe the sequence of events during each phase. List the phases of mitosis and describe the events characteristic of each phase. Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules, nonkinetochore microtubules, and asters. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Compare cytokinesis in animals and plants.
Describe the process of binary fission in bacteria and explain how eukaryotic mitosis may have evolved from binary fission. Explain how the abnormal cell division of cancerous cells escapes normal cell cycle controls. Distinguish between benign, malignant, and metastatic tumors. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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