The Cell Cycle. Chapter 12. Key Concepts in Chapter 12. Overview: The Key Roles of Cell Division. Video: Sea Urchin Embryonic Development (time-lapse)

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1 Chapter 12 The Cell Cycle Dr. Wendy era Houston Community College Biology 1406 Key Concepts in Chapter Most cell division results in genetically identical daughter cells. 2. The mitotic phase alternates with interphase in the cell cycle. 3. The eukaryotic cell cycle is regulated by a molecular control system. 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 Video: ea Urchin Embryonic Development (time-lapse) The continuity of life is based on the reproduction of cells, or cell division Cell Theory: Cells arise from preexisting cells or Every cell from a cell (Virchow in 1855) Chromosomes (blue) are moved by cell machinery (red) during division of a rat 2014 Pearson Education, kangaroo Inc. cell. Overview: The Key Roles of Cell Division, cont. In unicellular organisms, division of one cell reproduces the entire organism Multicellular eukaryotes depend on cell division for multiple functions: Development from a fertilized cell Growth (a) Reproduction 100 μm Figure 12.2 The functions of cell division 50 μm Repair Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division (c) Tissue renewal 20 µm (b) Growth and development 1

2 Concept 12.1: Most cell division results in genetically identical daughter cells Most cell division results in daughter cells with identical genetic information (DNA). This is mitosis. The exception is meiosis, a special type of division that can produce sperm and egg cells (i.e., non-identical daughter cells) This is the topic of Chapter 13 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 Figure 12.3 Eukaryotic chromosomes Cellular Organization of the Genetic Material, cont. 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 (non-reproductive cells) have two sets of chromosomes (called 2N or diploid) 20 μm Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells (called 1N or haploid) Distribution of Chromosomes During Eukaryotic Cell Division In preparation for cell division, DNA is replicated and the chromosomes condense Figure 12.4 A highly condensed, duplicated human chromosome (EM). Each duplicated chromosome has two sister chromatids (joined copies of the original chromosome), attached along their lengths by cohesins The centromere is the narrow waist of the duplicated chromosome, where the two chromatids are most closely attached ister chromatids Centromere 0.5 μm 2

3 Distribution of Chromosomes During Eukaryotic Cell Division, cont. During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei Once separate, the chromatids are called chromosomes Figures 12.5 Chromosome duplication and distribution Chromosomes Centromere Chromosome arm Chromosome duplication ister chromatids Chromosomal DNA molecules eparation of sister chromatids Eukaryotic Cell Division Eukaryotic cell division consists of Mitosis, the division of the genetic material in the nucleus Cytokinesis, the division of the cytoplasm 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 Phases of the Cell Cycle Figure 12.6 The cell cycle The cell cycle consists of two phases: Mitotic (M) phase (mitosis and cytokinesis) Interphase (cell growth and copying of chromosomes in preparation for cell division) (DNA synthesis) G 2 3

4 10 μm 10 μm Phases of the Cell Cycle, cont. Interphase (about 90% of the cell cycle) can be divided into subphases: phase ( first gap ) phase ( synthesis ) G 2 phase ( second gap ) The cell grows during all three phases, but chromosomes are duplicated only during the phase Figure 12.6 The cell cycle (DNA synthesis) G 2 Mitosis in an Animal Cell Mitosis is conventionally divided into five phases: Prophase Prometaphase Metaphase G 2 of Interphase Centrosomes Chromosomes (with centriole (duplicated, pairs) uncondensed) Prophase Early mitotic Aster spindle Centromere Prometaphase Fragments Nonkinetochore of nuclear microtubules envelope Anaphase Telophase Cytokinesis is well underway by late telophase Nucleolus Nuclear envelope Plasma membrane Two sister chromatids of one chromosome Kinetochore Kinetochore microtubule Video: Microtubules in Anaphase Metaphase Metaphase plate Anaphase Telophase and Cytokinesis Cleavage Nucleolus furrow forming pindle Daughter chromosomes Centrosome at one spindle pole Nuclear envelope forming 4

5 BioFlix: Mitosis Video: Animal Mitosis (time-lapse) 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 Mitotic pindle, cont. An aster (a radial array of short microtubules) extends from each centrosome The mitotic spindle includes the centrosomes, the spindle microtubules, and the asters The centrosome replicates during interphase, forming two centrosomes that migrate to opposite ends of the cell during prophase and prometaphase Figure 12.8 The mitotic spindle at metaphase ister chromatids Aster Centrosome Metaphase plate (imaginary) Kinetochores Microtubules Overlapping nonkinetochore microtubules Chromosomes Kinetochore microtubules Centrosome 1 µm 0.5 µm 5

6 The Mitotic pindle, cont. Video: pindle Formation During Mitosis 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, a plane midway between the spindle s two poles The Mitotic pindle, cont. In anaphase, the cohesins are cleaved by an enzyme called separase ister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell The microtubules shorten by depolymerizing at their kinetochore ends The Mitotic pindle, cont. Non-kinetochore 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 Cytokinesis: A Closer Look Figure Cytokinesis in animal and plant cells (a) Cleavage of an animal cell (EM) (b) Cell plate formation in a plant cell (TEM) In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow In plant cells, a cell plate forms during cytokinesis Cleavage furrow 100 µm Vesicles forming cell plate Wall of parent cell 1 µm Cell plate New cell wall Contractile ring of microfilaments Daughter cells Daughter cells 6

7 10 µm Animation: Cytokinesis Video: Myosin and Cytokinesis Nucleus Chromosomes Nucleolus condensing Chromosomes Figure Mitosis in a plant cell Binary Fission in Bacteria Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission 1 Prophase 2 Prometaphase Cell plate 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 Metaphase Anaphase Telophase Figure Bacterial cell division by binary fission 1 Chromosome replication begins. Origin of replication Two copies of origin E. coli cell Cell wall Plasma membrane Bacterial chromosome 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 2 One copy of the origin is now at each end of the cell. Origin Origin 3 Replication finishes. These differences result from regulation at the molecular level Cancer cells manage to escape the usual controls on the cell cycle 4 Two daughter cells result. 7

8 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 Experiment Results Figure Do molecular signals in the cytoplasm regulate the cell cycle? Experiment 1 Experiment 2 M nucleus immediately entered phase and DNA was synthesized. M nucleus began mitosis without chromosome duplication. M Conclusion Molecules present in the cytoplasm control the progression to and M phases. 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 Figure Mechanical analogy for the cell cycle control system checkpoint Control system The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received M G 2 M checkpoint G 2 checkpoint 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) The activity of a Cdk rises and falls with changes in concentration of its cyclin partner MPF (maturation-promoting factor) is a cyclin-cdk complex that triggers a cell s passage past the G 2 checkpoint into the M phase Figure Molecular control of the cell cycle at the G 2 checkpoint M G 2 M G 2 M MPF activity Time Cyclin concentration (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle Degraded cyclin Cdk Cyclin is degraded MPF Cdk Cyclin G 2 checkpoint (b) Molecular mechanisms that help regulate the cell cycle 8

9 top and Go igns: Internal and External ignals at the Checkpoints Many signals registered at checkpoints come from cellular surveillance mechanisms within the cell Checkpoints also register signals from outside the cell Three important checkpoints are those in, G 2, and M phases top and Go igns: Internal and External ignals at the Checkpoints, cont. For many cells, the checkpoint seems to be the most important If a cell receives a go-ahead signal at the checkpoint, it will usually complete the, G 2, and M phases and divide If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a non-dividing state called the G 0 phase Figure 12.17a Two important checkpoints checkpoint G 0 top and Go igns: Internal and External ignals at the Checkpoints, cont. An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase. Without go-ahead signal, cell enters G 0. (a) checkpoint With go-ahead signal, cell continues cell cycle. This mechanism assures that daughter cells have the correct number of chromosomes Figure 12.17b Two important checkpoints top and Go igns: Internal and External ignals at the Checkpoints, cont. M checkpoint Without full chromosome attachment, stop signal is received. (b) M checkpoint Prometaphase M G 2 Anaphase M G 2 G 2 checkpoint Metaphase With full chromosome attachment, go-ahead signal is received. External factors that influence cell division include specific growth factors. Growth factors are released by certain cells and stimulate other cells to divide For example, platelet-derived growth factor (PDGF) is made by blood cell fragments called platelets PDGF stimulates the division of human fibroblast cells in culture (PDGF binds to receptor tyrosine kinases; triggers a signal transduction pathway, allowing cells to pass the G1 checkpoint and divide). Platelets release PDGF during injury triggering fibroblasts to grow. 9

10 10 µm 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. calpels 4 PDGF is added to half the vessels. Figure The effect of plateletderived growth factor (PDGF) on cell division Without PDGF With PDGF Cultured fibroblasts (EM) top and Go igns: Internal and External ignals at the Checkpoints, cont. In density-dependent inhibition, crowded cells will stop dividing Most cells also exhibit anchorage dependence to divide, they must be attached to a substratum Density-dependent inhibition and anchorage dependence check the growth of cells at an optimal density Cancer cells exhibit neither type of regulation of their division Figure Density-dependent inhibition and anchorage dependence of cell division 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 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 1. They may make their own growth factor 2. They may convey a growth factor s signal without the presence of the growth factor 3. They may have an abnormal cell cycle control system Cancer and the HELA Cell Line Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence Example: The HeLa cell line has been reproducing in culture since 1951 they are basically immortal cells! Cells came from a tumor removed from a woman named Henrietta Lacks. Loss of Cell Cycle Controls in Cancer Cells, cont. A normal cell is converted to a cancerous cell by a process called transformation Cancer cells that are not eliminated by the immune system can 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 10

11 5 µm Loss of Cell Cycle Controls in Cancer Cells, cont. Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors Localized tumors may be treated with high-energy radiation, which damages the DNA in the cancer cells To treat metastatic cancers, chemotherapies that target the cell cycle may be used Figure The growth and metastasis of a malignant breast tumor Tumor Glandular tissue 1 A tumor grows 2 Cancer cells invade 3 from a single neighboring tissue. cancer cell. Cancer cells spread through lymph and blood vessels to other parts of the body. Lymph vessel Blood vessel Cancer cell Breast cancer cell (colorized EM) Metastatic tumor 4 A small percentage of cancer cells may metastasize to another part of the body. Advances in Treatment of Breast Cancer 1 out of 8 women will develop breast cancer. 10% of breast cancer cases are in men. Mitosis in Animal Cells (LM) 11