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Chapter 5 The Cell Cycle & Mitosis Control of the Cell Cycle Uncontrolled Cell Growth & Cancer http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter2/animation__how_the_cell_cycle_works.html 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 Review: Surface Area to Volume Ratio • Organisms must exchange matter with the environment to grow, reproduce and maintain organization. • The cellular surface-to-volume ratio affects a biological system’s ability to obtain resources and eliminate waste products. – As cells increase in volume, the relative surface area decreases and demand for material resources increases; – Large organisms require more cellular structures to adequately exchange materials and energy with the environment; – These limitations restrict cell size – the surface area of the plasma membrane must be large enough to adequately exchange materials; – Smaller cells have a more favorable surface-to-volume ratio for exchange of materials with the environment. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Overview: The Key Roles of Cell Division • 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 Cell Division • Most cell division results in daughter cells with identical genetic information, DNA • MITOSIS • A special type of division produces nonidentical daughter cells (gametes, or sperm and egg cells) • MEIOSIS 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 Cellular Organization of the Genetic Material • 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 Cellular Organization of the Genetic Material Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 12-4 0.5 µm Chromosomes Chromosome arm DNA molecules Chromosome duplication (including DNA synthesis) Centromere Sister chromatids Separation of sister chromatids Centromere Sister chromatids Mitosis v. Meiosis • Eukaryotic cell division consists of: – Mitosis, the division of the nucleus – Cytokinesis, the division of the cytoplasm – Alternating with interphase in the cell cycle, mitosis followed by cytokinesis provides a mechanism in which each daughter cell receives an identical and a complete complement of chromosomes. – Mitosis ensures fidelity in the transmission of heritable information, and production of identical progeny allows organisms to grow, replace cells, and reproduce asexually. • Sexual reproduction, however, involves the recombination of heritable information from both parents through fusion of gametes during fertilization. – 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. – Meiosis followed by fertilization provides a spectrum of possible phenotypes in offspring and on which natural selection operates. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Phases of the Cell Cycle • The cell cycle is a complex set of stages that is highly regulated with checkpoints, which determine the ultimate fate of the cell. • The cell cycle consists of – Interphase (cell growth, synthesis of DNA and preparation for division/mitosis) – Mitotic (M) phase (mitosis and cytokinesis) • Mitosis alternates with interphase in the cell cycle to pass a complete genome from the parent cell to daughter cells. • http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter2/animation__ how_the_cell_cycle_works.html Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Events of the Cell Cycle Nuclear division (M phase) cell divides Interphase (period of rest and preparation) is divided into 3 phases: 1. G1 – cell growth 2. S – DNA replication 3. G2 – preparation for Mitosis *During Interphase, chromosomes are in their “uncondensed” form and are called chromatin. Mitosis (division of the nucleus) occurs in 4 phases: 1. P = prophase – chromatin condenses into chromosomes, the centrioles separate & nuclear membrane breaks down 2. M = metaphase – chromosomes line up across center of cell and each chromosome is connected to a spindle fiber at its centromere 3. A = anaphase – sister chromatids separate into individual chromosomes and are pulled apart 4. T = telophase – chromosomes gather at opposite ends of the cell and 2 new nuclear membranes form around them *During mitosis, chromosomes are in their “uncondensed” form and are called chromatin. Cytokinesis – division of cytoplasm – well underway by late telophase 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 Review: The Cell Cycle • Mitosis passes a complete genome from the parent cell to daughter cells. – Mitosis occurs after DNA replication during interphase/S phase. – Mitosis followed by cytokinesis produces two genetically identical daughter cells. – Mitosis plays a role in growth, repair, and asexual reproduction. – Mitosis is a continuous process with observable structural features along the mitotic process (replication, alignment, separation). – Mitosis alternates with interphase in the cell cycle. – The entire cell cycle is directed by internal controls or checkpoints. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings The Mitotic Spindle: A Closer Look • Many of the events of mitosis depend on the mitotic spindle, which begins to form in the cytoplasm during prophase. • The mitotic spindle consists of fibers made of microtubules and associated proteins. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 12-7 Aster Centrosome Sister chromatids Microtubules Chromosomes Metaphase plate Kinetochores Centrosome 1 µm Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 µm Fig. 12-9: Cytokinesis – A Closer Look 100 µm Cleavage furrow Contractile ring of microfilaments Vesicles forming cell plate Wall of parent cell Cell plate 1 µm New cell wall Daughter cells (a) Cleavage of an animal cell (SEM) Daughter cells (b) Cell plate formation in a plant cell (TEM) Mitosis in Animal Cell Mitosis in Plant Cell Nucleus Nucleolus 1 Prophase Chromatin condensing Chromosomes 2 Prometaphase 3 Metaphase Cell plate 4 Anaphase 5 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 Concept 12.3: Control of the Cell Cycle • How do cells know when to divide? Cell division in eukaryotes is highly complex. Some mechanisms of cell cycle control include: – Presence of proteins called cyclins (internal regulators and external regulators): • Internal Regulators: respond to events inside the cell – hold cell in interphase until all chromosomes are copied. • External Regulators: respond to events outside the cell and direct cells to speed up or slow down the cell cycle. – Closeness of neighboring cells: • Density-dependence inhibition causes cells to stop dividing when they come in close contact with each other. • Anchorage dependence allows cells to divide only when anchored to a substrate. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Cell Cycle Checkpoints http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter2/animation__control_of_the_cell_cycle.html At each of these checkpoints, the cell checks that it has completed all of the tasks needed and is ready to proceed to the next step in its cycle. THESE CELL CYCLE CHECKPOINTS FUNCTION TO ENSURE THAT COMPLETE GENOMES ARE TRANSMITTED TO DAUGHTER CELLS! Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings KINASES: The Protein Regulators of the Cell Cycle • Cell Division is tightly controlled by complexes made of several specific proteins. – These complexes contain enzymes called cyclin-dependent kinases (CDKs), which turn on or off the various processes that take place in cell division. – CDK partners with a family of proteins called cyclins. – One such complex formed by the fusion of CDK and cyclin is mitosis-promoting factor (MPF), sometimes called maturationpromoting factor, which contains cyclin A or B and cyclindependent kinases (CDK). – CDK is activated when it is bound to cyclin (thus producing MPF), interacting with various other proteins that, in this case, allow the cell to proceed from G2 to mitosis. – The levels of cyclin change during the cell cycle, shutting on and off the mitotic phases. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings MPF and Cell Cycle Control at G2 Checkpoint http://www.sinauer.com/cooper5e/animation1604.html Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Growth Factors and Cell Cycle Control • EXTERNAL factors, both chemical and physical, can influence cell division. • Even when all other conditions are favorable, most mammalian cells divide only in the presence of specific growth factors. • Growth factors are proteins that are released by certain cells that stimulate other cells to divide. – These are local regulators – they travel short distances influence only cells in close vicinity. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings PDGF and Cell Cycle Control Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Contact Cell Cycle Control • Contact cell cycle control mechanisms include density-dependent inhibition and anchorage dependence. – In density-dependent inhibition, crowded cells stop dividing. – Anchorage dependence is a phenomenon in which cells must be attached to a substratum (i.e. extracellular matrix of a tissue) 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 Loss of Cell Cycle Controls in Cancer Cells • The cell cycle is regulated very precisely. Mutations in cell cycle genes that interfere with proper cell cycle control are found very often in cancer cells. • Cancer cells do not respond normally to the body’s control: – They exhibit neither density-dependent inhibition nor anchorage dependence. – They may not need growth factors to grow and divide. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Cancer Cells and the Formation of Tumors • 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 http://www.youtube.com/watch?v=IeUANxFVXKc Lymph vessel Tumor Blood vessel Cancer cell Metastatic tumor Glandular tissue 1 A tumor grows from a single cancer cell. 2 Cancer cells invade neighboring 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.