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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 [r]

Chapter 12 The Cell Cycle PowerPoint® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 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 Fig 12-1 • 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig 12-2 100 µm (a) Reproduction 20 µm 200 µm (b) Growth and development (c) Tissue renewal Fig 12-2a 100 µm (a) Reproduction Fig 12-2b 200 µm (b) Growth and development Fig 12-2c 20 µm (c) Tissue renewal Concept 12.1: Cell division results in genetically identical daughter cells • Most cell division results in daughter cells with identical genetic information, DNA • A special type of division produces nonidentical daughter cells (gametes, or sperm and egg cells) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 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 Fig 12-3 20 µm • 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 • 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 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 Fig 12-4 0.5 µm Chromosomes Chromosome arm Centromere DNA molecules Chromosome duplication (including DNA synthesis) Sister chromatids Separation of sister chromatids Centromere Sister chromatids • 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 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 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) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings • 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 Fig 12-5 S (DNA synthesis) G1 M ito si s in k to y C is s e MIT (M) OTIC PHA SE G2 • Mitosis is conventionally divided into five phases: – Prophase – Prometaphase – Metaphase – Anaphase – Telophase • Cytokinesis is well underway by late telophase BioFlix: Mitosis Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig 12-6 G2 of Interphase Centrosomes Chromatin (with centriole (duplicated) pairs) Prophase Early mitotic Aster Centromere spindle Nucleolus Nuclear Plasma envelope membrane Chromosome, consisting of two sister chromatids Metaphase Prometaphase Fragments Nonkinetochore of nuclear microtubules envelope Kinetochore Kinetochore microtubule Anaphase Cleavage furrow Metaphase plate Spindle Centrosome at one spindle pole Telophase and Cytokinesis Daughter chromosomes Nuclear envelope forming Nucleolus forming Fig 12-6a G2 of Interphase Prophase Prometaphase Fig 12-6b G2 of Interphase Chromatin Centrosomes (with centriole (duplicated) pairs) Prophase Early mitotic Aster spindle Nucleolus Nuclear Plasma envelope membrane Prometaphase Centromere Chromosome, consisting of two sister chromatids Fragments of nuclear envelope Kinetochore Nonkinetochore microtubules Kinetochore microtubule Fig 12-6c Metaphase Anaphase Telophase and Cytokinesis Fig 12-6d Metaphase Anaphase Metaphase plate Spindle Centrosome at one spindle pole Telophase and Cytokinesis Cleavage furrow Daughter chromosomes Nuclear envelope forming Nucleolus forming The Mitotic Spindle: A Closer Look • 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings • 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 • 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, the midway point between the spindle’s two poles Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig 12-7 Aster Centrosome Sister chromatids Microtubules Chromosomes Metaphase plate Kinetochores Centrosome µm Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 µm • 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig 12-8 EXPERIMENT Kinetochore Spindle pole Mark RESULTS CONCLUSION Chromosome movement Motor Microtubule protein Chromosome Kinetochore Tubulin subunits Fig 12-8a EXPERIMENT Kinetochore Spindle pole Mark RESULTS Fig 12-8b CONCLUSION Chromosome movement Microtubule Motor protein Chromosome Kinetochore Tubulin Subunits • 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 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 Video: Animal Mitosis Video: Sea Urchin (Time Lapse) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig 12-9 100 µm Cleavage furrow Contractile ring of microfilaments Vesicles forming cell plate Wall of parent cell Cell plate µm New cell wall Daughter cells (a) Cleavage of an animal cell (SEM) Daughter cells (b) Cell plate formation in a plant cell (TEM) Fig 12-9a 100 µm Cleavage furrow Contractile ring of microfilaments Daughter cells (a) Cleavage of an animal cell (SEM) Fig 12-9b Vesicles forming cell plate Wall of parent cell Cell plate µm New cell wall Daughter cells (b) Cell plate formation in a plant cell (TEM) Fig 12-10 Nucleus Nucleolus Prophase Chromatin condensing Chromosomes Prometaphase Metaphase Cell plate Anaphase Telophase 10 µm Fig 12-10a Nucleus Nucleolus Prophase Chromatin condensing Fig 12-10b Chromosomes Prometaphase Fig 12-10c Metaphase Fig 12-10d Anaphase Fig 12-10e Cell plate Telophase 10 µm 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 Fig 12-11-1 Origin of replication E coli cell Two copies of origin Cell wall Plasma membrane Bacterial chromosome Fig 12-11-2 Origin of replication E coli cell Two copies of origin Origin Cell wall Plasma membrane Bacterial chromosome Origin Fig 12-11-3 Origin of replication E coli cell Two copies of origin Origin Cell wall Plasma membrane Bacterial chromosome Origin Fig 12-11-4 Origin of replication E coli cell Two copies of origin Origin Cell wall Plasma membrane Bacterial chromosome Origin 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 Fig 12-12 Bacterial chromosome (a) Bacteria Chromosomes Microtubules (b) Dinoflagellates Intact nuclear envelope Kinetochore microtubule Intact nuclear envelope (c) Diatoms and yeasts Kinetochore microtubule Fragments of nuclear envelope (d) Most eukaryotes Fig 12-12ab Bacterial chromosome (a) Bacteria Chromosomes Microtubules (b) Dinoflagellates Intact nuclear envelope Fig 12-12cd Kinetochore microtubule Intact nuclear envelope (c) Diatoms and yeasts Kinetochore microtubule (d) Most eukaryotes Fragments of nuclear envelope 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 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 Fig 12-13 EXPERIMENT Experiment S G1 Experiment M G1 RESULTS S S 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 M M 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 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 Fig 12-14 G1 checkpoint Control system G1 M G2 M checkpoint G2 checkpoint S • 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 Fig 12-15 G0 G1 checkpoint G1 (a) Cell receives a go-ahead signal G1 (b) Cell does not receive a go-ahead signal The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases • Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclindependent kinases (Cdks) • The activity of cyclins and Cdks fluctuates during the cell cycle • MPF (maturation-promoting factor) is a cyclinCdk 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 Fig 12-16 30 20 10 100 200 300 Time (min) 400 500 % of dividing cells (– ) Protein kinase activity (– ) RESULTS Fig 12-17 M S G1 G2 M G1 S G2 M G1 MPF activity Cyclin concentration Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle Cdk Degraded cyclin M G2 G2 Cdk checkpoint Cyclin is degraded MPF Cyclin (b) Molecular mechanisms that help regulate the cell cycle Cyclin accumulation S G1 Fig 12-17a M G1 S G2 M G1 S G2 M G1 MPF activity Cyclin concentration Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle Fig 12-17b G Degraded cyclin M G2 G2 Cdk checkpoint Cyclin is degraded MPF Cyclin (b) Molecular mechanisms that help regulate the cell cycle Cyclin accumulation S Cdk 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 Fig 12-18 Scalpels Petri plate Without PDGF cells fail to divide With PDGF cells proliferate Cultured fibroblasts 10 µm • Another example of external signals is densitydependent 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 Fig 12-19 Anchorage dependence Density-dependent inhibition Density-dependent inhibition 25 µm 25 µm (a) Normal mammalian cells (b) Cancer cells • Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Loss of Cell Cycle Controls in Cancer Cells • Cancer cells 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 • 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 Fig 12-20 Lymph vessel Tumor Blood vessel Cancer cell Metastatic tumor Glandular tissue A tumor grows from a single cancer cell Cancer cells invade neighboring tissue Cancer cells spread to other parts of the body Cancer cells may survive and establish a new tumor in another part of the body Fig 12-UN1 G1 S Cytokinesis Mitosis G2 MITOTIC (M) PHASE Prophase Telophase and Cytokinesis Prometaphase Anaphase Metaphase Fig 12-UN2 Fig 12-UN3 Fig 12-UN4 Fig 12-UN5 Fig 12-UN6 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 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