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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 © 2014 Pearson Education, Inc. Chapter 9 Cell cycle I can: Describe the structure of the duplicated chromosome. Explain the cell cycle and stages of mitosis. Identify the stages of mitosis Explain the role of kinases and cyclin in the regulation of the cell cycle. Describe the loss of cell cycle control and cancer Figure 9.1 © 2014 Pearson Education, Inc. In unicellular organisms, division of one cell reproduces the entire organism Cell division enables multicellular eukaryotes to develop from a single cell and, once fully grown, to renew, repair, or replace cells as needed Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division © 2014 Pearson Education, Inc. Figure 9.2 100 m 200 m (a) Reproduction (b) Growth and development 20 m (c) Tissue renewal © 2014 Pearson Education, Inc. Concept 9.1: Most cell division results in genetically identical daughter cells Most cell division results in the distribution of identical genetic material—DNA—to two daughter cells © 2014 Pearson Education, Inc. Genome = all of a cell’s genetic info (DNA) Prokaryote: single, circular chromosome Eukaryote: more than one linear chromosomes Eg. Human:46 chromosomes, mouse: 40, fruit fly: 8 Somatic Cells Gametes Body cells Sex cells (sperm/egg) Diploid (2n): 2 of each type of chromosome Haploid (n): 1 of each type of chromosome Divide by meiosis Divide by mitosis Humans: n = 23 Humans: 2n = 46 Each chromosome must be duplicated before cell division Duplicated chromosome = 2 sister chromatids attached by a centromere Figure 9.5-1 Chromosomes 1 Chromosomal DNA molecules Centromere Chromosome arm © 2014 Pearson Education, Inc. Figure 9.5-2 Chromosomes 1 Chromosomal DNA molecules Centromere Chromosome arm Chromosome duplication 2 Sister chromatids © 2014 Pearson Education, Inc. Figure 9.5-3 Chromosomes 1 Chromosomal DNA molecules Centromere Parent cell Chromosome arm Chromosome duplication 2 Sister chromatids Two identical daughter cells © 2014 Pearson Education, Inc. Separation of sister chromatids 3 Chromosomes in Dividing Cells Duplicated chromosomes are called chromatids & are held together by the centromere © 2014 Pearson Education, Inc. Called Sister Chromatids 13 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 © 2014 Pearson Education, Inc. Phases of the Cell Cycle The mitotic phase alternates with interphase: G1 S G2 mitosis cytokinesis Interphase (90% of cell cycle) G1 Phase: cell grows and carries out normal functions S Phase: duplicates chromosomes G2 Phase: prepares for cell division M Phase (mitotic) Mitosis: nucleus divides Cytokinesis: cytoplasm divides Phases of the Cell Cycle The cell cycle consists of Mitotic (M) phase, including mitosis and cytokinesis Interphase, including cell growth and copying of chromosomes in preparation for cell division © 2014 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 © 2014 Pearson Education, Inc. Control of the Cell Cycle G1 Checkpoint - Check to see if DNA is damaged G2 Checkpoint - Check to see if DNA is replicated properly M Checkpoint - spindle assembly checkpoint, check for alignment of chromosomes Apoptosis - programmed cell death, if any of the checks fail Mitosis is conventionally divided into five phases Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis overlaps the latter stages of mitosis © 2014 Pearson Education, Inc. Mitosis Continuous process with observable structural features: Chromosomes become visible (prophase) Alignment at the equator (metaphase) Separation of sister chromatids (anaphase) Form two daughter cells (telophase & cytokinesis) © 2014 Pearson Education, Inc. 10 m Figure 9.7a G2 of Interphase Centrosomes (with centriole pairs) Nucleolus Chromosomes Early mitotic Centromere (duplicated, spindle Aster uncondensed) Nuclear envelope © 2014 Pearson Education, Inc. Prophase Plasma membrane Two sister chromatids of one chromosome Prometaphase Fragments of nuclear envelope Kinetochore Nonkinetochore microtubules Kinetochore microtubule 10 m Figure 9.7b Metaphase Anaphase Metaphase plate Spindle Centrosome at one spindle pole © 2014 Pearson Education, Inc. Telophase and Cytokinesis Cleavage furrow Daughter chromosomes Nuclear envelope forming Nucleolus forming Figure 9.7c G2 of Interphase Centrosomes (with centriole pairs) Chromosomes (duplicated, uncondensed) Nucleolus Nuclear envelope © 2014 Pearson Education, Inc. Plasma membrane Prophase Early mitotic Centromere spindle Aster Two sister chromatids of one chromosome Figure 9.7d Prometaphase Fragments of nuclear envelope Kinetochore © 2014 Pearson Education, Inc. Metaphase Nonkinetochore microtubules Kinetochore microtubule Metaphase plate Spindle Centrosome at one spindle pole Figure 9.7e Telophase and Cytokinesis Anaphase Cleavage furrow Daughter chromosomes © 2014 Pearson Education, Inc. Nuclear envelope forming Nucleolus forming Cytokinesis Cytoplasm of cell divided Animal Cells: cleavage furrow Plant Cells: cell plate forms © 2014 Pearson Education, Inc. 10 m Figure 9.7f G2 of Interphase © 2014 Pearson Education, Inc. 10 m Figure 9.7g Prophase © 2014 Pearson Education, Inc. 10 m Figure 9.7h Prometaphase © 2014 Pearson Education, Inc. 10 m Figure 9.7i Metaphase © 2014 Pearson Education, Inc. 10 m Figure 9.7j Anaphase © 2014 Pearson Education, Inc. 10 m Figure 9.7k Telophase and Cytokinesis © 2014 Pearson Education, Inc. The Mitotic Spindle: A Closer Look The mitotic spindle is a structure made of microtubules and associated proteins It controls chromosome movement during mitosis In animal cells, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center © 2014 Pearson Education, Inc. The centrosome replicates during interphase, forming two centrosomes that migrate to opposite ends of the cell during prophase and prometaphase An aster (radial array of short microtubules) extends from each centrosome The spindle includes the centrosomes, the spindle microtubules, and the asters © 2014 Pearson Education, Inc. During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes Kinetochores are protein complexes that are located on the centromere At metaphase, the centromeres of all the chromosomes are at the metaphase plate, an imaginary structure at the midway point between the spindle’s two poles © 2014 Pearson Education, Inc. Figure 9.8 Aster Sister chromatids Centrosome Metaphase plate (imaginary) Kinetochores Microtubules Chromosomes Overlapping nonkinetochore microtubules Kinetochore microtubules 1 m 0.5 m © 2014 Pearson Education, Inc. Centrosome Figure 9.8a Microtubules Chromosomes 1 m Centrosome © 2014 Pearson Education, Inc. Figure 9.8b Kinetochores Kinetochore microtubules 0.5 m © 2014 Pearson Education, Inc. 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 Chromosomes are also “reeled in” by motor proteins at spindle poles, and microtubules depolymerize after they pass by the motor proteins © 2014 Pearson Education, Inc. Figure 9.9 Experiment Results Kinetochore Spindle pole Conclusion Mark Chromosome movement Motor protein Chromosome Microtubule © 2014 Pearson Education, Inc. Kinetochore Tubulin subunits Figure 9.9a Experiment Kinetochore Spindle pole Mark © 2014 Pearson Education, Inc. Figure 9.9b Results Conclusion Chromosome movement Motor Microtubule protein Chromosome © 2014 Pearson Education, Inc. Kinetochore Tubulin subunits • During anaphase chromosome movement is correlated with kinetechore microtubules shortening at their kinetechore ends and not the spindle pole ends © 2014 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 © 2014 Pearson Education, Inc. Figure 9.10a (a) Cleavage of an animal cell (SEM) Cleavage furrow Contractile ring of microfilaments © 2014 Pearson Education, Inc. 100 m Daughter cells Cytokinesis in animal vs. plant cells Figure 9.10ba Vesicles forming cell plate © 2014 Pearson Education, Inc. Wall of parent cell 1 m Figure 9.11 Nucleus Chromosomes Nucleolus condensing Chromosomes 10 m 1 Prophase 2 Prometaphase Cell plate 3 Metaphase © 2014 Pearson Education, Inc. 4 Anaphase 5 Telophase • mitosis video • mitosis phases video © 2014 Pearson Education, Inc. Types of Cell Reproduction Asexual reproduction involves a single cell dividing to make 2 new, identical daughter cells Mitosis & binary fission are examples of asexual reproduction Sexual reproduction involves two cells (egg & sperm) joining to make a new cell (zygote) that is NOT identical to the original cells Meiosis is an example 50 Binary Fission in Bacteria Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission In E. coli, the single chromosome replicates, beginning at the origin of replication The two daughter chromosomes actively move apart while the cell elongates The plasma membrane pinches inward, dividing the cell into two © 2014 Pearson Education, Inc. Figure 9.12-1 Origin of replication E. coli cell 1 Chromosome replication begins. © 2014 Pearson Education, Inc. Two copies of origin Cell wall Plasma membrane Bacterial chromosome Figure 9.12-2 Origin of replication E. coli cell 1 Chromosome replication begins. 2 One copy of the origin is now at each end of the cell. © 2014 Pearson Education, Inc. Two copies of origin Origin Cell wall Plasma membrane Bacterial chromosome Origin Figure 9.12-3 Origin of replication E. coli cell 1 Chromosome replication begins. 2 One copy of the origin is now at each end of the cell. 3 Replication finishes. © 2014 Pearson Education, Inc. Two copies of origin Origin Cell wall Plasma membrane Bacterial chromosome Origin Figure 9.12-4 Origin of replication E. coli cell 1 Chromosome replication begins. 2 One copy of the origin is now at each end of the cell. 3 Replication finishes. 4 Two daughter cells result. © 2014 Pearson Education, Inc. 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 (dinoflagellates, diatoms, and some yeasts) exhibit types of cell division that seem intermediate between binary fission and mitosis © 2014 Pearson Education, Inc. Figure 9.13 Chromosomes Microtubules Intact nuclear envelope (a) Dinoflagellates Kinetochore microtubule Intact nuclear envelope (b) Diatoms and some yeasts © 2014 Pearson Education, Inc. Concept 9.3: 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 © 2014 Pearson Education, Inc. Evidence for Cytoplasmic Signals The cell cycle is driven by specific signaling molecules present in the cytoplasm Some evidence for this hypothesis comes from experiments with cultured mammalian cells Cells at different phases of the cell cycle were fused to form a single cell with two nuclei at different stages Cytoplasmic signals from one of the cells could cause the nucleus from the second cell to enter the “wrong” stage of the cell cycle © 2014 Pearson Education, Inc. Figure 9.14 Experiment Experiment 1 S G1 Experiment 2 M G1 Results S S G1 nucleus immediately entered S phase and DNA was synthesized. M M G1 nucleus began mitosis without chromosome duplication. Conclusion Molecules present in the cytoplasm control the progression to S and M phases. © 2014 Pearson Education, Inc. Checkpoints of 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 timing device of a washing machine 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 © 2014 Pearson Education, Inc. Figure 9.15 G1 checkpoint Control system G1 M G2 M checkpoint G2 checkpoint © 2014 Pearson Education, Inc. S 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 © 2014 Pearson Education, Inc. Figure 9.16 G1 checkpoint G0 G1 G1 Without go-ahead signal, cell enters G0. (a) G1 checkpoint S M G1 With go-ahead signal, cell continues cell cycle. G2 G1 G1 M G2 M G2 M checkpoint Prometaphase Without full chromosome attachment, stop signal is received. (b) M checkpoint © 2014 Pearson Education, Inc. Anaphase G2 checkpoint Metaphase With full chromosome attachment, go-ahead signal is received. Figure 9.16a G1 checkpoint G0 G1 Without go-ahead signal, cell enters G0. (a) G1 checkpoint © 2014 Pearson Education, Inc. G1 With go-ahead signal, cell continues cell cycle. Figure 9.16b G1 G1 M G2 M G2 M checkpoint Prometaphase Without full chromosome attachment, stop signal is received. (b) M checkpoint © 2014 Pearson Education, Inc. Anaphase G2 checkpoint Metaphase With full chromosome attachment, go-ahead signal is received. The cell cycle is regulated by a set of regulatory proteins and protein complexes including kinases and proteins called cyclins © 2014 Pearson Education, Inc. An example of an internal signal occurs at the M phase checkpoint In this case, anaphase does not begin if any kinetochores remain unattached to spindle microtubules Attachment of all of the kinetochores activates a regulatory complex, which then activates the enzyme separase Separase allows sister chromatids to separate, triggering the onset of anaphase © 2014 Pearson Education, Inc. 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 © 2014 Pearson Education, Inc. Figure 9.17-1 Scalpels 1 A sample of human connective tissue is cut up into small pieces. Petri dish © 2014 Pearson Education, Inc. Figure 9.17-2 Scalpels 1 A sample of human connective tissue is cut up into small pieces. Petri dish 2 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. © 2014 Pearson Education, Inc. Figure 9.17-3 Scalpels 1 A sample of human connective tissue is cut up into small pieces. Petri dish 2 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. 3 Cells are transferred to culture vessels. 4 PDGF is added to half the vessels. © 2014 Pearson Education, Inc. Figure 9.17-4 Scalpels 1 A sample of human connective tissue is cut up into small pieces. Petri dish 2 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. 3 Cells are transferred to culture vessels. 4 PDGF is added to half the vessels. Without PDGF © 2014 Pearson Education, Inc. With PDGF Cultured fibroblasts (SEM) 10 m Figure 9.17a Cultured fibroblasts (SEM) © 2014 Pearson Education, Inc. 10 m 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 Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence © 2014 Pearson Education, Inc. Figure 9.18 Anchorage dependence: cells require a surface for division Density-dependent inhibition: cells form a single layer Density-dependent inhibition: cells divide to fill a gap and then stop 20 m (a) Normal mammalian cells © 2014 Pearson Education, Inc. 20 m (b) Cancer cells Figure 9.18a 20 m (a) Normal mammalian cells © 2014 Pearson Education, Inc. Figure 9.18b 20 m (b) Cancer cells © 2014 Pearson Education, Inc. 9.3 The Cell Cycle and Cancer neoplasm: abnormal growth of cells benign: non-cancerous malignant: cancerous Cancer: cellular growth disorder that results from the mutation of genes that regulate the cell cycle Cancer cells ●lack differentiation ●have abnormal nuclei ●form tumors ●undergo metastasis © 2014 Pearson Education, Inc. Loss of Cell Cycle Controls in Cancer Cells Cancer cells do not respond to signals that normally regulate the cell cycle 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 © 2014 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 © 2014 Pearson Education, Inc. 5 m Figure 9.19 Breast cancer cell (colorized SEM) Lymph vessel Metastatic tumor Tumor Blood vessel Cancer cell Glandular tissue 1 A tumor grows from a single cancer cell. © 2014 Pearson Education, Inc. 2 Cancer cells invade neighboring tissue. 3 Cancer cells spread through lymph and blood vessels to other parts of the body. 4 A small percentage of cancer cells may metastasize to another part of the body. Figure 9.19a Tumor Glandular tissue 1 A tumor grows from a single cancer cell. © 2014 Pearson Education, Inc. 2 Cancer cells invade neighboring tissue. 3 Cancer cells spread through lymph and blood vessels to other parts of the body. Figure 9.19b Lymph vessel Metastatic tumor Blood vessel Cancer cell 3 Cancer cells spread through lymph and blood vessels to other parts of the body. © 2014 Pearson Education, Inc. 4 A small percentage of cancer cells may metastasize to another part of the body. 5 m Figure 9.19c Breast cancer cell (colorized SEM) © 2014 Pearson Education, Inc. Recent advances in understanding the cell cycle and cell cycle signaling have led to advances in cancer treatment Medical treatments for cancer are becoming more “personalized” to an individual patient’s tumor One of the big lessons in cancer research is how complex cancer is © 2014 Pearson Education, Inc. Figure 9.UN01 Control 200 A B C Treated A B C Number of cells 160 120 80 40 0 0 200 400 600 0 200 400 600 Amount of fluorescence per cell (fluorescence units) © 2014 Pearson Education, Inc. Figure 9.UN02 G1 S Cytokinesis Mitosis G2 MITOTIC (M) PHASE Prophase Telophase and Cytokinesis Prometaphase Anaphase Metaphase © 2014 Pearson Education, Inc. Figure 9.UN03 Test your Understanding # 6 p 190 © 2014 Pearson Education, Inc. Ch. 9 Understanding Check What is the correct phase of the cell cycle/mitosis for the following: A. Most cells that no longer divide or rarely divide are in this phase B. Sister chromatids separate and move apart C. Mitotic spindle begins to form D. Cell plate or cleavage furrow form E. Chromosomes replicate F. Chromosomes line up on equatorial plate G. Nuclear membrane forms H. Chromosomes become visible © 2014 Pearson Education, Inc. Ch 9 Understanding check 1. 2. 3. 4. Compare sexual to asexual reproduction. Compare/contrast mitosis to meiosis. Describe the events of meiosis. Define: genome, gametes, chromatin, chromosome, centromere, kinetochore, checkpoint, Cdk, MPF 5. What is the longest part of the cell cycle? Why? 6. If the diploid number is 46, what is the haploid number? 7. At the end of mitosis and cytokinesis, how do daughter cells compare with their parent cell when it was in G1? © 2014 Pearson Education, Inc. Understanding Check 1. A cell’s DNA was measured at 5 picograms. DNA levels range from 3-6 pgms in the cell cycle . What stage of the cell cycle is this cell in. How do you know? 2. At metaphase, if the haploid number is 3, how many chromatids does this cell have? 3. How do we know the cell uses chemical signals? 4. Summarize the cell control system. 5. Compare a cancer cell to a normal cell. What goes wrong? © 2014 Pearson Education, Inc. More Check 1. How do we know the cell uses chemical signals? 2. Summarize the cell control system. 3. Compare a cancer cell to a normal cell. What goes wrong? © 2014 Pearson Education, Inc. Test Yourself over Mitosis © 2014 Pearson Education, Inc. 94 Mitosis Quiz © 2014 Pearson Education, Inc. 95 Mitosis quiz answers • • • • • • • • • • A.-centrioles k.-nuclear envelope fragments B.- asters l. –nonkinetechore microtubules C.- chromatin m.-chromosome D.- nucleolus n.-centriole E.- nuclear envelope o.- kinetechore microtubules F.- plasma membrane G.-spindle microtubules (kinetechore microtubules) H.-centrioles I.-centromere/kinetechore J.-chromatid © 2014 Pearson Education, Inc. Mitosis Quiz © 2014 Pearson Education, Inc. 97 • • • • • • P.- spindle Q.-metaphase plate(equator) R. daughter chromosomes S. cleavage furrow T.- nucleus forming U.- nuclear envelope forming © 2014 Pearson Education, Inc. Name the Stages of Mitosis: Early Anaphase Early prophase Metaphase Interphase Late Prophase © 2014 Pearson Education, Inc. Late telophase, Mid-Prophase Advanced cytokinesis Early Telophase, Begin cytokinesis Late Anaphase Locate the Four Mitotic Stages in Plants Anaphase Telophase Metaphase Prophase © 2014 Pearson Education, Inc. • cell division bozeman • cell cycle interactive • cell cycle animations • Cell cycle game © 2014 Pearson Education, Inc.