The Cell Cycle Lecture Presentation PDF
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Uploaded by LuxuriantNovaculite5466
California State University, Northridge
Cindy S. Malone, PhD
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Summary
This presentation covers the cell cycle, mitosis, and meiosis. It details the process of cell division, chromosome duplication, and the different phases (prophase, prometaphase, metaphase, anaphase, telophase) involved in mitosis. The document also explains the concept of sister chromatids and the role of the spindle apparatus.
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12 The Cell Cycle Lecture Presentation by Cindy S. Malone, PhD, California State University Northridge © 2017 Pearson Education, L...
12 The Cell Cycle Lecture Presentation by Cindy S. Malone, PhD, California State University Northridge © 2017 Pearson Education, Ltd. Chapter 12 Opening Roadmap. © 2017 Pearson Education, Ltd. Introduction to the Cell Cycle Cells arise through cell division of preexisting cells Observations of newly developing organisms, or embryos, confirmed that plants and animals Start life as single-celled embryos Grow through a series of cell divisions Meiosis produces reproductive cells, called gametes Mitosis produces all other cell types = somatic cells © 2017 Pearson Education, Ltd. Introduction to the Cell Cycle Mitosis and meiosis are usually accompanied by cytokinesis Division of the cytoplasm into two daughter cells During mitosis, the genetic material is copied and divided equally between two cells Daughter cells are genetically identical to the parent cell and to each other Meiosis produces cells with half the amount of hereditary material as the parent cell Daughter cells are genetically different © 2017 Pearson Education, Ltd. How Do Cells Replicate? Cells must replicate for life to exist Basic steps in cellular replication: 1. Copying the DNA 2. Separating the copies 3. Dividing the cytoplasm to create two complete cells © 2017 Pearson Education, Ltd. What Is a Chromosome? A chromosome is a single long double helix of DNA wrapped around proteins called histones DNA encodes the cell’s genetic information A gene is a section of DNA Codes for a specific RNA Therefore codes for a specific protein © 2017 Pearson Education, Ltd. What Is a Chromosome? Before mitosis, each chromosome is replicated Each double-stranded DNA copy is called a chromatid At first, chromatids are attached along their entire length by proteins called cohesions Once mitosis begins, they are attached only at the centromere Chromatids attached at the centromere are called sister chromatids Two attached sister chromatids are still considered a single chromosome © 2017 Pearson Education, Ltd. Figure 12.1 Unreplicated chromosome Gene 1 Unreplicated Consists of a single, long DNA chromosome double helix wrapped around proteins (which are too small to distinguish at this scale). 1 µm Gene 1 Replicated chromosome Copy of gene 1 Consists of two copies of the same DNA double helix. Condensed replicated chromosome Gene 1 Sister chromatids Consists of DNA condensed around its associated proteins, resulting in a compact chromosome that Centromere 1 µm is 10,000 times shorter than its original length. Copy of gene 1 © 2017 Pearson Education, Ltd. Cells Alternate between M Phase and Interphase Growing cells cycle between two phases: 1. A dividing phase called the M (mitotic) phase Chromosomes are condensed into compact structures 2. A nondividing phase called interphase Chromosomes are uncoiled Cells are growing and preparing or are fulfilling their specialized functions Cells spend most of their time in interphase © 2017 Pearson Education, Ltd. The Discovery of S Phase Chromosome replication occurs only during interphase The stage in which DNA replication occurs is called the S (synthesis) phase The cell cycle is The orderly sequence of events That occurs from the formation of a eukaryotic cell Through the duplication of its chromosomes To the time it undergoes cell division © 2017 Pearson Education, Ltd. The Discovery of the Gap Phases Interphase also includes two gap phases, during which no DNA synthesis occurs G1 phase is the first gap Occurs between the M phase and the S phase G2 phase is the second gap Occurs between the S phase and mitosis The gap phases allow cells to grow and replicate organelles © 2017 Pearson Education, Ltd. Figure 12.2 Period when at least some of Radioactive thymidine labeled cells are in M phase Mitosis that are labeled (%) Gap between end of S Cells undergoing pulse and start of M phase First labeled cells enter mitosis M Indicates direction of progression through Time since end of thymidine pulse (hours) the cell cycle gap gap? M M M M M M M M Red tracks progress S of labeled cells S S S S S S S S through cell cycle © 2017 Pearson Education, Ltd. Figure 12.3 DIVISION (M) M G2 G1 S INTERPHASE (G1+ S +G2) © 2017 Pearson Education, Ltd. Web Activity: The Four Phases of the Cell Cycle © 2017 Pearson Education, Ltd. What Happens during M Phase? M phase consists of two distinct events: 1. Mitosis—the division of the replicated chromosomes 2. Cytokinesis—the division of the cytoplasm Every species has a characteristic number of chromosomes Humans have 46 chromosomes © 2017 Pearson Education, Ltd. What Happens during M Phase? Eukaryotic chromosomes consist of DNA wrapped around histone proteins This DNA-protein material is called chromatin During interphase, chromatin is in a “relaxed” state Chromosomes replicate during S phase Each chromosome now consists of two sister chromatids Exact copies of the same genetic information © 2017 Pearson Education, Ltd. Events in Mitosis Mitosis begins when chromatin condenses During mitosis The two sister chromatids separate to form independent daughter chromosomes One copy of each chromosome goes to each of the two daughter cells Each daughter cell receives a copy of the genetic information that is contained in each chromosome © 2017 Pearson Education, Ltd. Figure 12.4 INTERPHASE M PHASE Daughter cells G1 PHASE S PHASE G2 PHASE Parent cell Parent cell Parent cell Sister chromatids 4 unreplicated chromosomes 4 replicated chromosomes, At start of mitosis, (chromosomes are shown each consisting of two sister replicated partially condensed to make chromatids chromosomes During mitosis, sister them visible) condense. chromatids separate. Two daughter cells are formed by cytokinesis. © 2017 Pearson Education, Ltd. Cell Biology Video: Mitosis © 2017 Pearson Education, Ltd. Events in Mitosis Mitosis (M phase) is a continuous process with five subphases 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase © 2017 Pearson Education, Ltd. Prophase During prophase Chromosomes condense First become visible in the light microscope The spindle apparatus forms Produces mechanical forces that 1. Move replicated chromosomes during early mitosis 2. Pull chromatids apart in late mitosis © 2017 Pearson Education, Ltd. Prophase The spindle apparatus is made of microtubules Forms from microtubule-organizing centers (MTOCs) MTOCs define the two poles of the spindle apparatus Plus ends of microtubules grow out from each pole Polar microtubules extend from each spindle pole and overlap with each other In animal cells, MTOCs are centrosomes, each containing a pair of centrioles © 2017 Pearson Education, Ltd. Prometaphase During prometaphase The nuclear envelope breaks down Microtubules attach to chromosomes at kinetochores Structures that form at the centromere Two form on opposite sides of each chromosome Microtubules that attach to chromosomes are called kinetochore microtubules Chromosomes are pushed and pulled by microtubules until they reach the middle of the spindle © 2017 Pearson Education, Ltd. Metaphase During metaphase Formation of the mitotic spindle is completed Chromosomes are lined up on the metaphase plate —an imaginary plane between the two spindle poles Each chromosome is held by kinetochore microtubules from opposite poles Astral microtubules hold spindle poles in place © 2017 Pearson Education, Ltd. Figure 12.5-1 Sister chromatids separate; one chromosome copy goes to each daughter nucleus. Sister Kinetochore chromatids Centrioles Centrosomes Chromosomes Early spindle apparatus Polar microtubules Kinetochore Astral microtubules microtubules 1. Interphase: After 2. Prophase: 3. Prometaphase: Nuclear 4. Metaphase: chromosome replication, Chromosomes condense, envelope breaks down. Chromosomes complete each chromosome is and spindle apparatus Microtubules contact migration to middle of cell. composed of two sister begins to form. chromosomes at chromatids. Centrosomes kinetochores. have replicated. © 2017 Pearson Education, Ltd. Anaphase During anaphase Cohesions holding sister chromatids together split Sister chromatids are pulled by the spindle fibers toward opposite poles of the cell Creates two identical sets of daughter chromosomes Two forces pull chromosomes apart: Kinetochore microtubules shrink Motor proteins of the polar microtubules push the two poles of the cell away from each other © 2017 Pearson Education, Ltd. Telophase During telophase A new nuclear envelope begins to form around each set of chromosomes The chromosomes begin to decondense Mitosis is complete when two independent nuclei have formed Cytokinesis typically occurs immediately after mitosis The cytoplasm divides to form two daughter cells © 2017 Pearson Education, Ltd. Figure 12.5-2 Cytoplasm is divided. 5. Anaphase: Sister 6. Telophase: Nuclear 7. Cell division begins: 8. Cell division is chromatids separate into envelope re-forms, and Actin–myosin ring causes complete: Two daughter chromosomes, chromosomes plasma membrane to begin daughter cells form. which are pulled to opposite de-condense. pinching in. poles of spindle apparatus. © 2017 Pearson Education, Ltd. Web Activity: The Phases of Mitosis © 2017 Pearson Education, Ltd. How Do Chromosomes Move during Anaphase? Kinetochore microtubules Remain stationary during anaphase Shorten because tubulin subunits are lost from their plus ends Proteins from the kinetochore attach to a ring that surrounds the kinetochore microtubule As the plus end disassembles, the ring moves along the microtubule © 2017 Pearson Education, Ltd. Figure 12.6 How do kinetochore microtubules shorten to pull daughter chromosomes apart during anaphase? Microtubules shorten at the spindle pole. Microtubules shorten at the kinetochore. 1. Label targets: Use fluorescent labels to make the metaphase chromosomes fluoresce blue and the microtubules fluoresce yellow. 2. Mark microtubules: At the start of anaphase, darken sections of microtubules to mark them without changing their function. Daughter chromosomes will move toward the pole faster than the darkened sections. The darkened sections of the microtubules remained stationary as the chromosomes moved through them toward the pole. Kinetochore microtubules shorten at the kinetochore to pull daughter chromosomes apart during anaphase. © 2017 Pearson Education, Ltd. Figure 12.7 Kinetochore Kinetochore plates fibers Chromosome Microtubule Plus end Minus end Ring Chromosome movement Minus end Tubulin subunits © 2017 Pearson Education, Ltd. Cytokinesis Results in Two Daughter Cells Cytokinesis in plants Vesicles from the Golgi apparatus bring membrane and cell wall components to the middle of the cell These vesicles fuse to form a cell plate Cytokinesis in animals and many other eukaryotes A ring of actin and myosin filaments contracts inside the cell membrane Pinches inward to form a cleavage furrow Ring shrinks and tightens until division is complete © 2017 Pearson Education, Ltd. Figure 12.8 (a) Cytokinesis in plants (b) Cytokinesis in animals Microtubules direct vesicles to Actin–myosin center of spindle, interactions pinch where they fuse the plasma to divide the cell membrane in two in two Microtubule Cell plate Cleavage furrow 5 µm 100 µm © 2017 Pearson Education, Ltd. Table 12.1 © 2017 Pearson Education, Ltd. Bacterial Cell Replication Bacteria divide via binary fission This is a process similar to eukaryotic M phase Bacterial chromosomes are replicated Proteins attach to chromosomes and separate them Other proteins divide the cytoplasm © 2017 Pearson Education, Ltd. Figure 12.9 Protein filaments New DNA Original DNA Replication enzymes 1. DNA is copied, 2. DNA copies are 3. Ring of 4. Fission and protein separated; ring of protein draws complete. filaments attach. protein forms. in membrane. © 2017 Pearson Education, Ltd. Control of the Cell Cycle Cell-cycle length can vary greatly among cell types Mostly due to variation in the length of G1 phase Rapidly dividing cells essentially eliminate G1 phase Nondividing cells get permanently stuck in G 1 phase This arrested state is called the G0 state Division rate can also vary in response to changing conditions These variations in cell-cycle length suggest that the cell cycle is regulated © 2017 Pearson Education, Ltd. Figure 12.10 Is M phase controlled by regulatory molecules in the cytoplasm? Cytoplasmic regulatory molecules control entry into M phase. M-phase regulatory molecules are not in the cytoplasm or do not exist. M-phase Interphase cytoplasm cytoplasm Microinject cytoplasm from M-phase cell into one frog oocyte and cytoplasm from interphase cell into another frog oocyte. Only the oocyte injected with M-phase cytoplasm will begin M phase. Neither oocyte will begin M phase. Oocyte is driven into M phase (nuclear envelope begins to break down, spindle apparatus forms). Oocyte remains in G2 phase. M-phase cytoplasm contains a regulatory molecule that induces M phase in interphase cells. © 2017 Pearson Education, Ltd. MPF Contains a Protein Kinase and a Cyclin M phase-promoting factor (MPF) Is present in the cytoplasm of M-phase cells Induces mitosis in all eukaryotes MPF is composed of two distinct subunits: A protein kinase—enzyme that catalyzes the transfer of a phosphate group from ATP to a target protein A cyclin—protein that is present in different concentrations throughout the cell cycle © 2017 Pearson Education, Ltd. MPF Contains a Protein Kinase and a Cyclin The concentration of MPF cyclin Increases during interphase Peaks in M phase before decreasing again The MPF protein kinase is A cyclin-dependent kinase (Cdk) Active only when bound to the cyclin subunit When cyclin concentrations are high, MPF is active Target proteins are phosphorylated, initiating mitosis © 2017 Pearson Education, Ltd. Figure 12.11 M phase–promoting factor (MPF) Inhibitory phosphorylation site Cyclin is a Cyclin-dependent Cyclin Cdk regulatory kinase (Cdk) catalyzes protein phosphorylation of other P proteins to start M phase MPF component concentration MPF Cdk in cl Cy PF M G1 S G2 M phase G1 S G2 M phase G1 S Time © 2017 Pearson Education, Ltd. How Is MPF Turned On? MPF’s Cdk subunit has two phosphorylation sites Both are phosphorylated after cyclin binds Inhibits the kinase Late in G2 phase, one phosphate group is removed Activates the kinase Leads to chromosome condensation and formation of the mitotic spindle apparatus © 2017 Pearson Education, Ltd. How Is MPF Turned Off? MPF deactivation illustrates two key concepts about regulatory systems in cells: 1. N egative feedback occurs when a process is slowed or shut down by its products 2. Destroying specific proteins is a common way to control cell processes The enzyme complex that is activated during anaphase attaches proteins to the cyclin subunit Marks the subunit for destruction Leads to deactivation of MPF © 2017 Pearson Education, Ltd. Cell-Cycle Checkpoints Can Arrest the Cell Cycle Many other protein complexes are involved in regulating the cell cycle There are four cell-cycle checkpoints Critical points in the cell cycle that are regulated Regulatory molecules at each checkpoint allow a cell to “decide” whether to proceed with division If these regulatory molecules are defective, the checkpoint may fail Cells that divide without control may form a tumor © 2017 Pearson Education, Ltd. Figure 12.12 G2 checkpoint M-phase checkpoints Pass checkpoint if: Pass checkpoints if: chromosomes have 1. chromosomes have replicated successfully attached to spindle DNA is undamaged apparatus M activated MPF 2. chromosomes have is present properly segregated G2 and MPF is absent G1 S G0 G1 checkpoint Pass checkpoint if: Mature cells do not cell size is adequate pass this checkpoint nutrients are sufficient (they enter G0 state) social signals are present DNA is undamaged © 2017 Pearson Education, Ltd. G1 Checkpoint The first, most important, checkpoint occurs in late G1 Will the cell continue through the cycle and divide? Or will it exit the cycle and enter G0? Four factors affect passage through the G1 checkpoint 1. Size 2. Availability of nutrients 3. Social signals from other cells 4. Damage to DNA © 2017 Pearson Education, Ltd. G1 Checkpoint If DNA is physically damaged, the p53 protein Either activates proteins that pause the cell cycle until damage can be repaired Or initiates apoptosis = programmed cell death p53 is an example of a tumor suppressor Damage to the p53 gene can lead to uncontrolled cell division © 2017 Pearson Education, Ltd. G2 Checkpoint The second checkpoint is between the G2 and M phases If chromosome replication has not proceeded properly or if DNA is damaged Phosphate is not removed from MPF MPF is not activated Cells remain in G2 phase © 2017 Pearson Education, Ltd. M-phase Checkpoint The third and fourth checkpoints are during M phase 1. Between metaphase and anaphase Ensures that sister chromatids do not split until all kinetochores are attached to the spindle apparatus 2. Between anaphase and telophase Ensures that chromosomes have fully separated The three cell-cycle checkpoints prevent the division of cells that are damaged or are in G0 © 2017 Pearson Education, Ltd. Figure 12.12 G2 checkpoint M-phase checkpoints Pass checkpoint if: Pass checkpoints if: chromosomes have 1. chromosomes have replicated successfully attached to spindle DNA is undamaged apparatus M activated MPF 2. chromosomes have is present properly segregated G2 and MPF is absent G1 S G0 G1 checkpoint Pass checkpoint if: Mature cells do not cell size is adequate pass this checkpoint nutrients are sufficient (they enter G0 state) social signals are present DNA is undamaged © 2017 Pearson Education, Ltd. Cancer: Out-of-Control Cell Division Cancer Forty percent of Americans will develop cancer A complex family of diseases caused by cells that Grow in an uncontrolled fashion Invade nearby tissues Spread to other sites in the body Over 200 types of cancer All arise from cells in which cell-cycle checkpoints have failed © 2017 Pearson Education, Ltd. Figure 12.13 Prostate Breast (female) Lung Colon & rectal Melanoma Cancer type Bladder Non-Hodgkin lymphoma Renal cell Thyroid Endometrial Leukemia Pancreatic Estimated new cases* Estimated deaths* *Annual incidence (2014) © 2017 Pearson Education, Ltd. Cancer: Out-of-Control Cell Division Cancerous cells have two types of defects: 1. Defects that activate the proteins required for cell growth when they should not be active 2. Defects that prevent tumor suppressor genes from shutting down the cell cycle © 2017 Pearson Education, Ltd. Properties of Cancer Cells Two types of tumors: Malignant tumors are cancerous and invasive Can spread throughout the body via the blood or lymph and initiate secondary tumors Called metastasis Benign tumors are noncancerous and noninvasive Many cancers are thought to arise from cells with defects in the G1 checkpoint © 2017 Pearson Education, Ltd. Figure 12.14 (a) Benign tumor Normal cells Blood vessel Benign tumor cells may continue to divide, but are not invasive (they do not spread from tumor) Lymphatic vessel (b) Malignant tumor Malignant tumor cells divide and spread to adjacent tissues and to distant tissues through lymphatic vessels and blood vessels Lymphatic vessel Blood vessel New tumor that has formed in distant tissue by metastasis © 2017 Pearson Education, Ltd. Social Control Cells respond to signals from other cells Divide only when it benefits the whole organism Social control is based on growth factors—small proteins that stimulate division Cells in culture will not grow unless serum—liquid portion of blood—is added Growth factors in serum allow cells to pass the G 1 checkpoint Cancer cells divide without growth factors © 2017 Pearson Education, Ltd. How Does the G1 Checkpoint Work? Growth factors stimulate production of E2F protein, which triggers expression of genes required for S phase G1 cyclins Rb protein is a tumor suppressor It suppresses E2F activity Keeps the cell in G0 © 2017 Pearson Education, Ltd. How Does the G1 Checkpoint Work? Growth factors help cells pass the G1 checkpoint 1. Growth factors arrive from other cells 2. Stimulate production of E2F and G1 cyclins 3. Rb inactivates E2F; G1 cyclins bind to Cdks 4. G1 cyclin–Cdk complex phosphorylates Rb 5. Rb releases E2F 6. E2F targets genes that get S phase under way © 2017 Pearson Education, Ltd. Figure 12.15 Cy Inactivating cli Cyclin n P phosphate Cyclin Cdk P G1 checkpoint P P li n passed yc Rb C Cyclin Cdk Activating P S-phase phosphate Rb Growth E2F factors E2F ATP E2 F E2F Rb ADP E 2F 2F E 1. Growth factors 2. Growth factors 3. Cyclin binds to 4. Inactivating 5. Phosphorylated 6. E2F triggers arrive from other cause increase in Cdk; Cdk is phosphate is removed, Rb releases E2F. production of cells. cyclin and E2F phosphorylated. and active Cdk S-phase proteins. concentrations. Rb inactivates E2F phosphorylates Rb. by binding to it. © 2017 Pearson Education, Ltd. How Do Social Controls and Cell-Cycle Checkpoints Fail? In some cancers, the G1 cyclin is overproduced Permanently activates Cdk Continuously phosphorylates Rb so it can’t bind E2F In some cancers, Rb is missing or defective Doesn’t bind to E2F E2F activates genes to start S phase © 2017 Pearson Education, Ltd.