Chapter 9 Notes Cell Division and Mitosis
Chapter 9 Notes Cell Division and Mitosis BIOL 04102-03
Northwest Missouri State University
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Date Created: 10/06/16
09.27.16 CHAPTER 9: CELL DIVISION AND MITOSIS DRIVING QUESTIONS 1. When and how does normal cell division occur in the body? 2. How do normal cells and cancer cells differ with respect to cell division? 3. How are cancer treatment decisions made for a given patient? 4. How are new cancer drugs developed? NATURE’S PHARMACY I. 1988, taxol was discovered to treat ovarian cancer. a. 30% of women saw their tumors shrink. II. 1990, taxol was more effective at treating breast cancer. a. 50% of patients saw their tumors regress. III. Pacific yew tree a. Pacific Northwest b. Would need 1.3 million lbs of bark for medicine c. Would kill 360k trees d. Not including breast cancer treatments POISON PILL I. Two ways to treat cancer: a. A disease of unregulated cell division: i. Cells divide inappropriately and accumulate. ii. Some instances form a tumor. b. Cut it out c. Radiation d. Methods worked well for some cancers, powerless with others. II. World War II: Soldiers exposed to mustard gas (poison) had lower white blood cell counts. a. Cells in bone marrow had stopped dividing. b. Cancer of bone marrow resulted from uncontrolled cell division, could poison be used as cancer treatment? i. Chemotherapy 1. Treatment of disease by chemicals. III. Researchers learned most treatments worked by interfering with cell division. a. The process by which a cell reproduces itself. b. Cell division is important for normal growth, development, and repair of an organism. INFOGRAPHIC 9.1: WHY DO CELLS DIVIDE? o Embryonic development o A fertilized egg and its daughter cells continue to divide to create the trillions of cells that makeup the human body. o Cell replacement o Most cells have a finite life span. o Cell division within tissues regularly replaces the dying cells and maintains healthy tissues. o Cells in bone marrow regularly divide to produce new, healthy blood cells. o The new cells migrate to the blood vessel to replace those that have reached the end of their life span. o Would healing o Injury triggers cell division to replace damaged cells. IV. To produce new cells, cells pass through a series of stages collectively known as the cell cycle. a. The ordered sequence of stages that a cell progresses through in order to divide during its life. i. Stages include preparatory phases 1. G1, S, G2 ii. Division phases 1. Mitosis 2. Cytokinesis b. One cell becomes two. c. Before a cell divides… i. Makes a copy of its contents. 1. So each new cell has the same amount of organelles, DNA, and cytoplasm as the original cell. d. The preparatory stage of the cell cycle is known as interphase. i. The stage of the cell cycle in which cells spend most of their time, preparing for cell division. ii. G1phase 1. Cell grows larger and begins to produce more cytoplasm and organelles. iii. Synthesis phase (S) 1. DNA replicates and chromosomes are duplicated. iv. G2phase 1. Cell is ready to enter the division phases. v. In a cell that takes 24 hours to divide, interphase takes about 22 hours to complete. e. Division phases of the cell cycle is called mitosis and cytokinesis. i. Mitosis 1. The segregation and separation of duplicated chromosomes during cell division. 2. When the chromosomes are evenly divided between the two daughter cells. 3. Duplicated chromosomes line up along the midline of the cell. 4. Each duplicated chromosome is made up of two identical sister chromatids connected at a region called the centromere. o Sister chromatids o The two identical DNA molecules that make up a duplicated chromosome following DNA replication. o Centromere o The specialized region of a chromosome where the sister chromatids are joined. 2 o Critical for proper alignment and separation of sister chromatids during mitosis. 5. The two sister chromatids are then pulled apart from each other. 6. Each chromatid will form one of two genetically identical chromosomes in a daughter cell. ii. Cytokinesis 1. The physical division of a cell into two daughter cells. 2. Two daughter cells physically separate. 3. The enlarged cell splits into two separate cells, each containing a full complement of organelles and DNA. iii. One parent divides into two new daughter cells, each one identical to the original parent cell. iv. Mitosis and cytokinesis take about 2 hours of a 24 hour time period. INFOGRAPHIC 9.2: THE CELL CYCLE- HOW CELLS REPRODUCE. The purpose of the cell cycle is to replicate cells, creating two new daughter cells that are genetically identical to the original parent cell. The cell cycle consists of preparatory phases collectively known as interphase, as well as division phases, mitosis and cytokinesis. I. Interphase a. The preparatory phases of the cell cycle. b. The cell makes a copy of the DNA and produces more organelles and cytoplasm. c. G1 phase i. The cell enlarges, produces additional cytoplasm, and begins to produce new organelles. d. S Phase i. DNA replication takes place. ii. Each chromosome is replicated to produce two identical sister chromatids. e. G2 Phase i. The final preparatory stage, during which the cell prepares for division. II. Mitosis a. The sister chromatids of each chromosome separate from each other, setting up the two identical nuclei of the daughter cells. III. Cytokinesis a. Daughter cells physically separate from each other. IV. The chromosome perspective a. Interphase i. Chromosome replication b. Mitosis i. Chromosome separation V. Most of todays chemotherapy drugs target one or more elements of the cell cycle. a. Interfere with ability to copy DNA b. Interfere with ability to separate their chromosomes WITCHES’ BREW 3 I. Plants have long been known to be rich sources of medicinal products. a. 1960, National Cancer Institution created a screening program. i. Tests plant compounds for their potential as chemotherapeutic drugs. b. 1960-1981, NCI-affiliated scientists screened more than 100k plant extracts. TABLE 9.1: DRUGS FROM PLANTS I. The well-established drugs listed below are among dozens that were developed after scientists began to analyze the chemical constituents of plants used by traditional peoples for medicinal or other purposes. a. Aspirin i. Reduces pain and inflammation ii. Meadowsweet b. Codeine i. Eases pain, suppresses coughing ii. Opium poppy c. Pseudoephedrine i. Reduces nasal congestion ii. Ephedra, ma huang II. August 1962, Taxus brevifolia, the pacific yew, is one of the species of a family of related evergreen trees. a. Found only in Washington, Oregon, and western Canada. b. Trash tree by timber industry. c. Poisonous. d. Killed cancer cells. FOR RESEARCHERS INVOLVED WITH THE PROJECT, THE MESSAGE WAS CLEAR: FIND A SOLUTION TO THE SUPPLY PROBLEM OR WATCH A PROMISING NEW DRUG GO UP IN SMOKE. III. 1971, Wall and Wani, chemists at the Research Triangle Institute in North Carolina, identified the specific chemical responsible for Taxus brevifolia’s effects. a. Taxol. “A STRUCTURE ONLY A TREE WOULD MAKE” I. 1977, Horwitz and Schiff studied the chemical for a month. a. Confirmed that small amounts of taxol killed cancer cells. b. The cells were loaded with long fibers known as microtubules. II. Microtubules are part of the cell’s cytoskeleton (Ch 3). a. Hollow protein fibers that are key components of the cytoskeleton and make up the fibers of the mitotic spindle. i. The structure that separates sister chromatids during mitosis. b. During interphase, microtubules are present as a vast network of fibers running throughout the cytoplasm of the cell. 4 c. As the cells enter the early stages of mitosis, the microtubules rearrange to form a structure called the mitotic spindle. d. The microtubules begin to attach to sister chromatids of duplicated chromosomes as a cell prepares to enter a phase of mitosis known as metaphase. e. The microtubules then tug at the sister chromatids from opposite sides of the cell, pulling them apart during anaphase. III. Microtubules attach to the sister chromatids at the kinetochore. a. Proteins located at the centromere that provide an attachment point for microtubules of the mitotic spindle. b. A collection of proteins on the centromere. c. The microtubules pull the sister chromatids apart by shortening at the end attached to the kinetochore end. i. Subunits are removed from this end, shortening it, and dragging the chromatid with it. d. The shortening pulls the sister chromatids to opposite ends of the cell. IV. Taxol interferes with the organization of microtubules and prevents them from shortening. a. The cells are unable to pull the sister chromatids apart and the cells arrest in metaphase. INFOGRAPHIC 9.3: TAXOL INTERFERES WITH MITOSIS I. S Phase a. Chromosomes are duplicated. b. The resulting sister chromatids are physically attached to each other at the centromere region of the DNA. c. Sister chromatids i. Duplicated DNA strands d. Microtubules i. Fibers that attach to the kinetochore. e. Centromere i. Where sister chromatids are attached. f. Kinetochore i. Proteins that connect the microtubules to the DNA II. Mitosis and Cytokinesis a. Microtubules shorten by disassembling at the kinetochore end, pulling the sister chromatids apart. b. Taxol keeps microtubules from shortening, so mitotic chromosomes can neither form proper attachments to the spindle nor be properly separated by spindle shortening. WHEN DIVISION RUNS AMOK: CANCER I. Cells divide only on demand, in response to growth signals. a. When cells no longer need to divide these growth signals are turned off. b. The cells pause in their life cycle and stop dividing. c. Cancer cells divide haphazardly. II. Cancer results when cells accumulate DNA sequence changes. 5 a. Every time a cell replicates its DNA there is a small chance it will make a mistake. i. Normally, mutations are caught by the cell and fixed at what’s known as a cell cycle checkpoint. 1. Mutations o A change in the nucleotide sequence of DNA. 2. Cell cycle checkpoint o A cellular mechanism that ensures that each stage of the cell cycle is completed accurately. 3. Cells have a series of checkpoints, which monitor each stage of the cell cycle and checks for mistakes. 4. Checkpoints also prevent progression of the cell cycle until previous stages have been successfully completed. ii. If problems are detected, two things can happen: 1. Either the cell ramps up DNA repair mechanisms, giving itself time to fix DNA mistakes. 2. In cases of severe or irreparable damage, the checkpoints direct a cell to commit suicide. o Apoptosis. o Programmed cell death. o Often referred to as cell suicide. INFOGRAPHIC 9.4: CELL DIVISION IS TIGHTLY REGULATED Normal cells have mechanisms to ensure that cell division is carried out precisely and only when necessary. Regulated cell division ensures that adequate cell number and healthy tissue structure are maintained in the body. I. Cell Cycle Checkpoints a. During the cell cycle, a system of checkpoints regulates a cell’s progress. b. Checkpoints prevent a cell from progressing to the next stage until it accurately finishes the current stage. II. Apoptosis a. When a normal cell sustains irreparable damage, it undergoes programmed cell death. b. This cellular suicide prevents cells from producing more damaged daughter cells. III. Even with these mechanisms, cells with mutations do manage to complete the cell cycle and divide. a. Especially likely if the mutations affect the genes that code for those proteins that function as checkpoints. b. When cells accumulate enough DNA damage to interfere with multiple checkpoints, the result is cancer. c. Cancer cells plow through the cell cycle uninhibited, divide uncontrollably, and in many cases eventually form a mass of cells called a tumor. i. A mass of cells resulting from uncontrolled cell division. INFOGRAPHIC 9.5: CANCER- WHEN CHECKPOINTS FAIL 6 Cancer cells have damaged checkpoint mechanisms, which enable them to divide when they should not. This means that DNA damage or errors in chromosome separation are passed on to daughter cells. These cells can bypass apoptosis. With each cell division, the damage is perpetuated and additional errors in DNA accumulate. I. Healthy cells divide periodically and correct DNA damage and mitotic mistakes. II. Cancer cells divide in an unregulated manner and accumulate DNA damage and make mitotic mistakes. IV. Cancer kills by crowding out normal cells and invading other organs, causing them to fail. a. Cancer cells also secrete chemicals that wreak havoc on the body’s biochemistry, with fatal complications. V. Ovarian cancer. a. No clear symptoms and no effective screening tests. b. When it is discovered, often the cancer is already spread. c. Usually recurs. d. Cure is rare. CHAPTER 9 SUMMARY o Cell division is a fundamental feature of life, necessary for normal growth, development, and repair of the body. o The cell cycle is the sequence of step that a cell undergoes in order to divide o Interphase, mitosis, cytokinesis. o During mitosis, replicated chromosomes segregate to opposite poles of the dividing cell. o During cytokinesis, the cell physically divides into two daughter cells. o Mitosis takes place in several phases, each of which is important to properly segregate chromosomes into daughter cells. o Cell cycle checkpoints ensure accurate progression through the cell cycle. o Repair mechanisms at each checkpoint can fix mistakes that occur. o DNA damage o In the absence of proper checkpoint function, cells can acquire DNA damage during cell division and pass these DNA defects on to daughter cells. o Mistakes in the course of cell division can lead to cancer. o Unregulated cell division. o Cancer cells have lost the ability to regulate cell division and reproduce uncontrollably. o Often forming a tumor. o Chemotherapy drugs work by interfering with some part of the cell cycle. o Taxol works by interfering with separation of sister chromatids by microtubules during mitosis. o Cancer is often treated with a combination of surgery, chemotherapy, and radiation. o Chemotherapy and radiation kill rapidly dividing cells in their path, including both cancer cells and healthy cells, which accounts for the toxicity and side effects of these treatments. 7 o Many drugs, including some of those used to treat cancer, are extracted from plants. o Basic scientific research, often funded by the government, is critical to the development of new drugs to treat cancer. 8
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