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LECTURE PREENTATION For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, teven A. Wasserman, Peter V. Minorsky, Robert B. Jackson Chapter 12 The Cell Cycle Overview: 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 Lectures by Erin Barley Kathleen Fitzpatrick Figure 12.2 100 µm (a) Reproduction 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 (b) Growth and development 200 µm 20 µm (c) Tissue renewal 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 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 1

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 omatic cells (nonreproductive cells) have two sets of chromosomes Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells 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), which separate during cell division The centromere is the narrow waist of the duplicated chromosome, where the two chromatids are most closely attached Figure 12.4 ister chromatids During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei Once separate, the chromatids are called chromosomes Centromere 0.5 µm Figure 12.5-3 1 Chromosomes Centromere Chromosomal DNA molecules 2 3 Chromosome arm Chromosome duplication (including DNA replication) and condensation ister chromatids eparation of sister chromatids into two chromosomes 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 only one set of chromosomes, half as many as the parent cell 2

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) Interphase (about 90% of the cell cycle) can be divided into subphases G 1 phase ( first gap ) phase ( synthesis ) phase ( second gap ) The cell grows during all three phases, but chromosomes are duplicated only during the phase Figure 12.6 INTERPHAE G 1 MITOTIC (M) PHAE Cytokinesis Mitosis (DNA synthesis) Mitosis is conventionally divided into five phases Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis overlaps the latter stages of mitosis Figure 12.7a Figure 12.7b of Interphase Prophase Prometaphase Centrosomes (with centriole pairs) Chromatin (duplicated) Early mitotic spindle Fragments Aster of nuclear envelope Centromere Nonkinetochore microtubules Metaphase Metaphase plate Anaphase Telophase and Cytokinesis Cleavage furrow Nucleolus forming Nucleolus Nuclear envelope Plasma membrane Chromosome, consisting of two sister chromatids Kinetochore Kinetochore microtubule pindle Centrosome at one spindle pole Daughter chromosomes Nuclear envelope forming 3

The Mitotic pindle: 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 An aster (a radial array of short microtubules) extends from each centrosome The spindle includes the centrosomes, the spindle microtubules, and the asters Figure 12.8 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, an imaginary structure at the midway point between the spindle s two poles ister chromatids Aster Overlapping nonkinetochore microtubules Kinetochore microtubules Centrosome Metaphase plate (imaginary) Kinetochores Microtubules Chromosomes Centrosome 1 µm 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 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 4

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 12.10a (a) Cleavage of an animal cell (EM) Cleavage furrow 100 µm Contractile ring of microfilaments Daughter cells Figure 12.10b (b) Cell plate formation in a plant cell (TEM) Figure 12.11 Nucleus Chromatin condensing Nucleolus Chromosomes Cell plate 10 µm Vesicles forming cell plate Wall of parent cell Cell plate 1 µm New cell wall 1 Prophase 2 Prometaphase 3 Metaphase 4 Anaphase 5 Telophase Daughter cells 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 Figure 12.12-4 1 2 3 Chromosome replication begins. Replication continues. Replication finishes. Origin of replication Two copies of origin E. coli cell Origin Cell wall Plasma membrane Bacterial chromosome Origin 4 Two daughter cells result. 5

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 Evidence for Cytoplasmic ignals The cell cycle appears to be driven by specific chemical signals present in the cytoplasm ome 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 Figure 12.14 EXPERIMENT Experiment 1 Experiment 2 REULT G 1 M G 1 When a cell in the phase was fused with a cell in G 1, the G 1 nucleus immediately entered the phase DNA was synthesized. M M When a cell in the M phase was fused with a cell in G 1, the G 1 nucleus immediately began mitosis a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. The Cell Cycle Control ystem 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 Figure 12.15 G 1 checkpoint G 1 M Control system 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,, 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 M checkpoint checkpoint 6

Figure 12.16 G 1 checkpoint (a) Cell receives a go-ahead signal. G 0 G 1 G 1 (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 cyclin-dependent kinases (Cdks) Cdks activity fluctuates during the cell cycle because it is controled by cyclins, so named because their concentrations vary with the cell cycle MPF (maturation-promoting factor) is a cyclin-cdk complex that triggers a cell s passage past the checkpoint into the M phase Figure 12.17 M G 1 M G 1 M G 1 MPF activity Cyclin concentration Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle Degraded cyclin Cdk Cyclin is degraded G 1 M checkpoint Cdk MPF Cyclin top and Go igns: Internal and External ignals at the Checkpoints An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase ome 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 (b) Molecular mechanisms that help regulate the cell cycle Figure 12.18 1 2 3 A sample of human connective tissue is cut up into small pieces. Petri dish Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. Cells are transferred to culture vessels. calpels 4 PDGF is added to half the vessels. 10 µm A clear 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 Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence Without PDGF With PDGF 7

Figure 12.19 Anchorage dependence Density-dependent inhibition Density-dependent inhibition 20 µm 20 µm (a) Normal mammalian cells (b) Cancer cells 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 Figure 12.UN01 E P HAE R T I N 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 Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors Telophase and Cytokinesis Cytokinesis Mitosis MITOTIC (M) PHAE Anaphase Metaphase G 1 Prometaphase Prophase Figure 12.UN02 Figure 12.UN03 8

Figure 12.UN04 Figure 12.UN05 Figure 12.UN06 9