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Chapter 12 The Cell Cycle
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Overview: The Key Roles of Cell Division
Fig. 12-1 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 Figure 12.1 How do a cell’s chromosomes change during cell division? In unicellular organisms, division of one cell reproduces the entire organism
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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 100 µm 200 µm 20 µm Figure 12.2 The functions of cell division (a) Reproduction (b) Growth and development (c) Tissue renewal
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Chromosomal reduction
Concept 12.1: Cell division results in genetically identical daughter cells A special type of division produces nonidentical daughter cells (gametes, or sperm and egg cells) Most cell division results in daughter cells with identical genetic information, DNA Eukaryotic cell division consists of: Mitosis, the division of the nucleus Cytokinesis, the division of the cytoplasm Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell Chromosomal reduction Chromosomal duplication Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells Somatic cells: (nonreproductive cells) have two sets of chromosomes
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Cellular Organization of the Genetic Material
Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division 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 Figure 12.3 Eukaryotic chromosomes 20 µm
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Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus
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Distribution of Chromosomes During Eukaryotic Cell Division
DNA molecules Chromosome 0.5 µm 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 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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Concept 12.2: The mitotic phase alternates with interphase in 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)
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Concept 12.2: The mitotic phase alternates with interphase in the cell cycle
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
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Concept 12.2: The mitotic phase alternates with interphase in the cell cycle
Mitosis is conventionally divided into five phases: Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis is well underway by late telophase
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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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In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis 1 2 6b 3 6a 5 4
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Fig. 12-UN5
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Telophase and Cytokinesis
The mitotic division of an animal cell G2 of Interphase Prophase Prometaphase Metaphase Anaphase Telophase and Cytokinesis Figure 12.6 The mitotic division of an animal cell
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Chromosome, consisting of two sister chromatids
The mitotic division of an animal cell The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis During prophase, 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 An aster (a radial array of short microtubules) extends from each centrosome The spindle includes the centrosomes, the spindle microtubules, and the asters During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes Figure 12.6 The mitotic division of an animal cell Chromatin (duplicated) Chromosome, consisting of two sister chromatids
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Chromosome, consisting of two sister chromatids
The mitotic division of an animal cell The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis During prophase, 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 An aster (a radial array of short microtubules) extends from each centrosome The spindle includes the centrosomes, the spindle microtubules, and the asters During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes 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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The mitotic division of an animal cell
At metaphase, the chromosomes are all lined up at the metaphase plate, the midway point between the spindle’s two poles 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
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Telophase and Cytokinesis
Video: Animal Mitosis The mitotic division of an animal cell At metaphase, the chromosomes are all lined up at the metaphase plate, the midway point between the spindle’s two poles 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 Metaphase Anaphase Telophase and Cytokinesis Nonkinetochore microtubules 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
Aster Centrosome Sister chromatids Microtubules Chromosomes Metaphase plate Kineto- chores Figure 12.7 The mitotic spindle at metaphase Centrosome 1 µm Overlapping nonkinetochore microtubules Kinetochore microtubules The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis 0.5 µm
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At which end do kinetochore microtubules shorten during anaphase?
EXPERIMENT Kinetochore Spindle pole 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 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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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 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 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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Mitosis in a plant cell 10 µm 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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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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Bacterial cell division by binary fission
Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Two copies of origin 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 Figure Bacterial cell division by binary fission
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Bacterial cell division by binary fission
Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Two copies of origin 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 Origin Origin Figure Bacterial cell division by binary fission
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Bacterial cell division by binary fission
Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Two copies of origin 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 Origin Origin Figure Bacterial cell division by binary fission
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Bacterial cell division by binary fission
Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Two copies of origin 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 Origin Origin Figure Bacterial cell division by binary fission
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The Evolution of Mitosis
Bacterial chromosome (a) Bacteria Chromosomes A hypothetical sequence for the evolution of mitosis Microtubules 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 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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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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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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 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 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 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 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)
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M G1 S G2 M G1 S G2 M G1 Fig. 12-17 MPF activity Cyclin concentration
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 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
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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Scalpels Petri plate Without PDGF cells fail to divide With PDGF
Fig 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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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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Density-dependent inhibition
Fig 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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Lymph vessel Tumor Blood vessel Cancer cell Glandular tissue
Fig 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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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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EXPERIMENT RESULTS Experiment 1 Experiment 2 S G1 M G1 S S M M
Fig EXPERIMENT Experiment 1 Experiment 2 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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Fig. 12-UN3
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Fig. 12-UN4
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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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Chromosome, consisting of two sister chromatids
Figure 12.6 The mitotic division of an animal cell 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 Daughter chromosomes Nuclear envelope forming Nucleolus Nuclear envelope Plasma membrane Chromosome, consisting of two sister chromatids Kinetochore Kinetochore microtubule Spindle Centrosome at one spindle pole
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Chromosome, consisting of two sister chromatids
G2 of Interphase G2 of Interphase Prophase Prophase Prometaphase 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 Telophase and Cytokinesis
Metaphase Anaphase Telophase and Cytokinesis 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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