E.Chapter12 - THE CELL CYCLE PDF

‫‪The Cell Cycle‬‬ ‫لجنة الطب البشري‬ 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...

‫‪The Cell Cycle‬‬ ‫لجنة الطب البشري‬ 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 © 2011 Pearson Education, Inc. Figure 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 © 2011 Pearson Education, Inc. Figure 12.2 100 m (a) Reproduction 200 m (b) Growth and development 20 m (c) Tissue renewal Figure 12.2a 100 m (a) Reproduction Figure 12.2b 200 m (b) Growth and development Figure 12.2c 20 m (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 © 2011 Pearson Education, Inc. 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 © 2011 Pearson Education, Inc. Figure 12.3 20 m  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 Somatic cells (nonreproductive cells) have two sets of chromosomes Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells © 2011 Pearson Education, Inc.  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 © 2011 Pearson Education, Inc. Figure 12.4 Sister chromatids Centromere 0.5 m  During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei Once separate, the chromatids are called chromosomes © 2011 Pearson Education, Inc. Figure 12.5-1 Chromosomal Chromosomes DNA molecules 1 Centromere Chromosome arm Figure 12.5-2 Chromosomal Chromosomes DNA molecules 1 Centromere Chromosome arm Chromosome duplication (including DNA replication) and condensation 2 Sister chromatids Figure 12.5-3 Chromosomal Chromosomes DNA molecules 1 Centromere Chromosome arm Chromosome duplication (including DNA replication) and condensation 2 Sister chromatids Separation of sister chromatids into two chromosomes 3  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 © 2011 Pearson Education, Inc. 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 © 2011 Pearson Education, Inc. 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) © 2011 Pearson Education, Inc.  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 © 2011 Pearson Education, Inc. Figure 12.6 INTERPHASE G1 S (DNA synthesis) G2  Mitosis is conventionally divided into five phases – Prophase – Prometaphase – Metaphase – Anaphase – Telophase Cytokinesis overlaps the latter stages of mitosis BioFlix: Mitosis © 2011 Pearson Education, Inc. Figure 12.7 10 m G2 of Interphase Prophase Prometaphase Metaphase Anaphase Telophase and Cytokinesis Centrosomes Chromatin Fragments Nonkinetochore (with centriole pairs) (duplicated) Early mitotic Aster of nuclear microtubules Metaphase Cleavage Nucleolus spindle Centromere envelope plate furrow forming Plasma Nucleolus Nuclear membrane Chromosome, consisting Kinetochore Kinetochore Nuclear envelope of two sister chromatids microtubule Spindle Centrosome at Daughter envelope one spindle pole chromosomes forming Figure 12.7a G2 of Interphase Prophase Prometaphase Centrosomes Fragments (with centriole Chromatin Early mitotic Aster of nuclear Nonkinetochore pairs) (duplicated) spindle envelope microtubules Centromere Plasma Nucleolus membrane Kinetochore Kinetochore Chromosome, consisting Nuclear of two sister chromatids microtubule envelope Figure 12.7b Metaphase Anaphase Telophase and Cytokinesis Metaphase Cleavage Nucleolus plate furrow forming Nuclear Spindle Centrosome at Daughter envelope one spindle pole chromosomes forming Figure 12.7c 10 m G2 of Interphase Prophase Prometaphase Figure 12.7d 10 m Metaphase Anaphase Telophase and Cytokinesis Figure 12.7e Figure 12.7f Figure 12.7g Figure 12.7h Figure 12.7i Figure 12.7j The Mitotic Spindle: 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 © 2011 Pearson Education, Inc.  An aster (a radial array of short microtubules) extends from each centrosome The spindle includes the centrosomes, the spindle microtubules, and the asters © 2011 Pearson Education, Inc.  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 © 2011 Pearson Education, Inc. Figure 12.8 Centrosome Aster Metaphase Sister plate chromatids (imaginary) Microtubules Chromosomes Kineto- chores Centrosome 1 m Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 m Figure 12.8a Kinetochores Kinetochore microtubules 0.5 m Figure 12.8b Microtubules Chromosomes Centrosome 1 m  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 © 2011 Pearson Education, Inc. Figure 12.9 EXPERIMENT Kinetochore Spindle pole Mark RESULTS CONCLUSION Chromosome movement Microtubule Kinetochore Motor protein Tubulin subunits Chromosome Figure 12.9a EXPERIMENT Kinetochore Spindle pole Mark RESULTS Figure 12.9b CONCLUSION Chromosome movement Microtubule Kinetochore Motor protein Tubulin subunits Chromosome  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 © 2011 Pearson Education, Inc. 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 © 2011 Pearson Education, Inc.  Video: Animal Mitosis Video: Sea Urchin (Time Lapse) © 2011 Pearson Education, Inc. Figure 12.10 (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM) 100 m Cleavage furrow Vesicles Wall of parent cell forming 1 m cell plate Cell plate New cell wall Contractile ring of Daughter cells microfilaments Daughter cells Figure 12.10a (a) Cleavage of an animal cell (SEM) 100 m Cleavage furrow Contractile ring of Daughter cells microfilaments Figure 12.10b (b) Cell plate formation in a plant cell (TEM) Vesicles Wall of parent cell 1 m forming cell plate Cell plate New cell wall Daughter cells Figure 12.10c Cleavage furrow 100 m Figure 12.10d Vesicles Wall of parent cell 1 m forming cell plate Figure 12.11 Chromatin Nucleus condensing 10 m Nucleolus Chromosomes Cell plate 1 Prophase 2 Prometaphase 3 Metaphase 4 Anaphase 5 Telophase Figure 12.11a Chromatin Nucleus condensing Nucleolus 10 m 1 Prophase Figure 12.11b Chromosomes 10 m 2 Prometaphase Figure 12.11c 10 m 3 Metaphase Figure 12.11d 10 m 4 Anaphase Figure 12.11e 10 m Cell plate 5 Telophase 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 © 2011 Pearson Education, Inc. Figure 12.12-1 Origin of Cell wall replication Plasma membrane E. coli cell Bacterial chromosome 1 Chromosome Two copies replication of origin begins. Figure 12.12-2 Origin of Cell wall replication Plasma membrane E. coli cell Bacterial chromosome 1 Chromosome Two copies replication of origin begins. 2 Replication Origin Origin continues. Figure 12.12-3 Origin of Cell wall replication Plasma membrane E. coli cell Bacterial chromosome 1 Chromosome Two copies replication of origin begins. 2 Replication Origin Origin continues. 3 Replication finishes. Figure 12.12-4 Origin of Cell wall replication Plasma membrane E. coli cell Bacterial chromosome 1 Chromosome Two copies replication of origin begins. 2 Replication Origin Origin continues. 3 Replication finishes. 4 Two daughter cells result. 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 © 2011 Pearson Education, Inc. Figure 12.13 Bacterial (a) Bacteria chromosome Chromosomes Microtubules (b) Dinoflagellates Intact nuclear envelope Kinetochore microtubule (c) Diatoms and some yeasts Intact nuclear envelope Kinetochore microtubule (d) Most eukaryotes Fragments of nuclear envelope Figure 12.13a Bacterial chromosome (a) Bacteria Chromosomes Microtubules Intact nuclear envelope (b) Dinoflagellates Figure 12.13b Kinetochore microtubule Intact nuclear envelope (c) Diatoms and some yeasts Kinetochore microtubule Fragments of nuclear envelope (d) Most eukaryotes 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 © 2011 Pearson Education, Inc. 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 © 2011 Pearson Education, Inc. Figure 12.14 EXPERIMENT Experiment 1 Experiment 2 S G1 M G1 RESULTS S S M M When a cell in the S When a cell in the phase was fused M phase was fused with with a cell in G1, a cell in G1, the G1 the G1 nucleus nucleus immediately immediately entered began mitosis—a spindle the S phase—DNA formed and chromatin was synthesized. 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 © 2011 Pearson Education, Inc. Figure 12.15 G1 checkpoint Control system S G1 M G2 M checkpoint G2 checkpoint  For many cells, the G1 checkpoint seems to be the most important 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 © 2011 Pearson Education, Inc. Figure 12.16 G0 G1 checkpoint G1 G1 (a) Cell receives a go-ahead (b) Cell does not receive a signal. 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 G2 checkpoint into the M phase © 2011 Pearson Education, Inc. Figure 12.17 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 Cdk Degraded cyclin G2 Cdk checkpoint Cyclin is degraded Cyclin MPF (b) Molecular mechanisms that help regulate the cell cycle Figure 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 Figure 12.17b Cdk Degraded cyclin G2 Cdk checkpoint Cyclin is degraded MPF Cyclin (b) Molecular mechanisms that help regulate the cell cycle 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 © 2011 Pearson Education, Inc. Figure 12.18 1 A sample of human Scalpels connective tissue is cut up into small pieces. Petri dish 2 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. 4 PDGF is added 10 m 3 Cells are transferred to to half the culture vessels. vessels. Without PDGF With PDGF Figure 12.18a 10 m  A clear 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 Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence © 2011 Pearson Education, Inc. Figure 12.19 Anchorage dependence Density-dependent inhibition Density-dependent inhibition 20 m 20 m (a) Normal mammalian cells (b) Cancer cells Figure 12.19a 20 m Figure 12.19b 20 m 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 © 2011 Pearson Education, Inc.  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 © 2011 Pearson Education, Inc. Figure 12.20 Lymph vessel Tumor Blood vessel Glandular Cancer tissue cell Metastatic tumor 1 A tumor grows 2 Cancer 3 Cancer cells spread 4 Cancer cells from a single cells invade through lymph and may survive cancer cell. neighboring blood vessels to and establish tissue. other parts of the a new tumor body. in another part of the body.  Recent advances in understanding the cell cycle and cell cycle signaling have led to advances in cancer treatment © 2011 Pearson Education, Inc. Figure 12.21 Figure 12.UN01 P G1 S Cytokinesis Mitosis G2 MITOTIC (M) PHASE Prophase Telophase and Cytokinesis Prometaphase Anaphase Metaphase Figure 12.UN02 Figure 12.UN03 Figure 12.UN04 Figure 12.UN05 Figure 12.UN06