Life Sci 15 - Ch. 8 Chromosomes & Cell Division - Reading Notes PDF

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Chapter 8 Chromosomes and Cell Division — Reading Notes: Week 3 Page 222 8.1 Immortal cells can spell trouble: cell division in sickness and in health Throughout most of your body your cells are continuously dying off, and the ones that remain divide and replace the cells you’ve lost, in an ongoing process. Animal cells have a sort of counter that reflects how many times the cell has divided. Telomere - A section of noncoding, repetitive DNA that serves as a protective cap and is located at each tip of every chromosome, right next to the genes that direct the processes that maintain the organism The counter aforementioned. Every time a cell divides, making an exact copy of itself, its DNA divides as well. However, etc time the DNA divides, the process by which chromosomes are duplicated causes the telomere at each end of every chromosome to get shorter. Eventually, the telomeres can become so short that additional cell divisions cause the loss of functional, essential DNA, and that means almost certain death for the cell. Some cells do rebuild their telomeres after each cell division, restoring the chromosome’s protective caps. Unfortunately, for most of the other types of cells that rebuild their telomeres with each cell division, the telomere rebuilding presents a big problem: the cells are unable to stop dividing. Such cells commonly go by another name: cancer. Page 223 Prokaryotes have one method of cell division (called binary fission), and it serves all of their cell division needs. Eukaryotes have 2 methods of cell division, mitosis and meiosis, each of which has a specific purpose in a eukaryote’s life cycle. Page 224 8.2 Some chromosomes are circular, others are linear All life on earth uses DNA to store genetic information. The most important part of a eukaryotic chromosome may be the DNA molecule, which carries information about how to accomplish the processes needed to support the life of the organism. The eukaryotic chromosome is composed of Chromatin, a linear DNA strand bound to and wrapped tightly around proteins called histones, which keep the DNA from getting tangled and enable it to be tightly and efficiently packed inside the nucleus. Most prokaryotes-the bacteria and archaea- have less DNA that eukaryotes.

They carry their genetic information in a single, circular chromosome, a close loop of double-stranded DNA that is attached at one site to the cell membrane. And when it is time for them to reproduce, they use a method called Binary Fission - which means “division in two” Binary Fission begins with Replication. Replication - the method by which a cell creates an exact duplicate of each chromosome. Replication in prokaryotes begins as the double-stranded DNA molecule unwinds from its coiled-up configuration. Once the strands are uncoiled, they split apart like a zipper, with bases exposed on each of the 2 separated, single-stranded, circular molecules of DNA. As the double-stranded molecule unzips, enzymes bind to the DNA and attache freefloating nucleotides to the growing DNA backbone, matching A to T and G to C, thus creating 2 identical double-stranded DNA molecules. Page 225 The original cell, called the Parent Cell, then pinches in somewhere between the 2 spots the 2 newly created circular chromosomes attach to, until it divides into 2 new cells, called Daughter Cells. Each of the Daughter Cells has an identical 2-stranded copy of the original 2-stranded circular chromosome. Binary Fission is considered Asexual Reproduction, because the Daughter Cells inherit their DNA from a single parent cell, and thus are genetically identical to the parent. Page 226 8.3 There is a time for everything in the eukaryotic cell cycle Eukaryotic cells don’t do every job at once. They go through phases. This alternation of activities between processes related to growth and process related to cell division is called the Cell Cycle. All the cells of a multicellular eukaryotic organism can be divided into 2 types: Somatic Cells - the cells forming the body of the organism; Reproductive Cells - Sex cells, i.e., the Gametes (sperm and eggs)- and the cells that give rise to them. The Cell Cycle describes the series of phases in Somatic Cell division. The 2 main phases in the Cell Cycle are Interphase - during which the cell grows and prepares to divide Mitotic Phase (or M Phase) - during which division occurs. Page 227 Interphase

Interphases is further divided into 3 distinct sub-cases Gap 1 (G1) During this period, a cell may grow and develop as well as perform its various cellular functions (making proteins, getting rid of waste, etc.) However, some cells enter a state called G0, which is a “resting” phase outside the Cell Cycle in which no cell division occurs. DNA Synthesis (S Phase) During this phase, the cell begins to prepare for cell division. First, it creates an exact duplicate of each chromosome by replication. Before replication, each chromosome’s DNA consists of a single long, linear molecule. After replication, each chromosome’s DNA has become a pair of identical long, linear molecules, held together near the center; the regions where the 2 pieces are in contact is called the Centromere. Gap 2 (G2) Significant growth occurs in this phase, along with high rates of protein synthesis in preparation for division. Gap 2 differs from Gap 1 in its shorter duration and its genetic material now existing in a duplicate. Mitotic Phase This period begins with Mitosis Mitosis - A process in which the parent cell’s nucleus, including its chromosome, divides. Mitosis is generally followed by Cytokinesis Cytokinesis - During which the cytoplasm is divided into 2 daughter cells. Each daughter cell has a complete set of the parent cell’s DNA and other cellular structures. The Mitotic Phase is usually the shortest period in the eukaryotic cell cycle. Rates of cell division are regulated by a Cell-Cycle Control System. Cell-Cycle Control System - A group of molecules, mostly proteins, within a cell that coordinates the events of the cell cycle. This Control System functions through a system of Checkpoints. Checkpoints - Critical points in the cell cycle at which progress is blocked- and cells are prevented from dividing- until specific signals trigger continuation of the process. The signals that trigger Cell-Cycle transitions commonly consist of Growth Factors. Growth Factors - Provide feedback about the cell’s environment and can signal

that division is appropriate. Checkpoints in the Cell Cycle make it possible for cells to: 1. reduce the likelihood of completing cell division when errors have occurred in the process 2. and repose to feedback conveying information about the cell’s internal and external environments. There are 3 primary Checkpoints that regulate the Cell Cycle in eukaryotes: 1. G1/S Checkpoint: Assessing DNA damage and cell growth. 1. Occurring near the end of the G1 phase, this is the point when a cell “decides” whether it will proceed to the S phase and complete cell division, or delay cell division, or enter into an extended “resting” phase, G0. 1. Although often described as an extended “resting” phase, G0 is, in fact, a non dividing, non-growing phase that may include great metabolic activity critical to an organism’s proper functioning. 2. A malfunction in the G1/S Checkpoint can prevent cells with damaged DNA from blocking their division, leading to cancer. 2. G2/M Checkpoint: Assessing DNA synthesis 1. Just before beginning Mitosis, a cell reaches the G2/M checkpoint. 1. This Checkpoint serves as a “mitosis-readiness” assessment. 3. Spindle assembly Checkpoint: Assessing anaphase readiness during mitosis. 1. This important Cell-Cycle Checkpoint occurs during Mitosis. 2. At this point, Cell-Cycle Control Mechanisms assess whether the chromosomes have aligned properly at the Metaphase Plate, and whether there is appropriate tension (pull) on them. 3. If this point is passed, then the cell completes cell division. Page 228 8.4 Cell division is preceded by chromosome replication. After all, every single time any cell in any organism’s body divides, that cell’s DNA must first duplicate itself so that each of the 3 new daughter cells has all of the genetic material of the original parent cell. The process of DNA replication, as we’ve seen, is called replication. Watson and Crick were referring to the feature of DNA called Complementarity Complementarity - Meaning, that in the double-stranded DNA molecule, the base on one strand always has the same pairing partner (called the Complementary Base) on the other strand: A pairs with T (and vice versa), and G pairs with C (and vice versa). With this consistent pattern of pairing, one strand carries all the information needed to construct its complementary strand. Just before cells divide, the DNA molecule unwinds and “unzips”, and each half of the unzipped molecule serves as a template on which the

missing half is reconstructed. At the end of the process of reconstructing the missing halves, there are 2 DNA molecules- each identical to the original DNA molecule- one for each of the 2 new cells. The structure of DNA dictates the directions along the linear molecule in which replication occurs. The individual units that make up DNA are nucleotides, which have 3 components: A nitrogen-containing molecule called a base A phosphate group and a molecule of 5-carbon sugar. Page 229 Each of the 5 carbon atoms in the sugar molecules is given a number. The nitrogenous base is attached to the 1’ (one prime) carbon An -OH group is attached to the 3’ carbon And the phosphate group is attached to the sugar’s 5' carbon atom The process of DNA replication occurs in 2 steps 1. Unwinding and separation of the 2 strands 2. Reconstruction and elongation of new, complementary strands. A feature of DNA that has important consequences for the process of replication is that its 2 strands run in opposite directions. 5’ to 3’ pattern in one strand 3’ to 5’ patten in the opposite strand. 1 Unwinding and Separation Replication begins at a specific site, called the Origin of Replication. Origin of Replication - Where the coiled, double-stranded DNA molecule unwinds and separates into 2 strands, like a zipper unzipping. In prokaryotes, there is a single Origin of Replication, while eukaryotes have multiple origin sites on each chromosome. At the Origin of Replication, a complex of proteins binds to the DNA. One of the proteins, an enzyme called DNA Helicase, unwinds the coiled DNA and separates the 2 complementary strands. The unwinding and separating of the 2 DNA strands creates what is called a Replication Fork Page 230 2 Reconstruction and Elongation At the Replication Form, a group of several proteins, called a Replication Complex, binds to each of the exposed strands. This complex includes the enzyme DNA Polymerase

DNA Polymerase - Adds DNA nucleotides with bases that are complementary to the bases on each exposed strand. Replication proceeds in both directions at once from each Origin of Replication The result of replication is 2 double-stranded DNA molecules that carry virtually the same genetic information. Note though, that the Daughter DNA Molecules are not completely identical DNA Proofreading and Error Correction Because DNA Polymerases perform proofreading functions as well as excision and repair functions, many of these errors are caught and repaired during or after replication or whenever they occur. If an error remains, the sequences in a replicated DNA molecules (including the genes) can be different from those in the parent molecule. A changed sequence may ultimately lead to the production of a different protein. Page 231 Most cells are not immortal: mitosis generates replacements Mitosis has just one purpose: to enable existing cells to generate new, genetically identical cells. There are 2 different reasons for this need. 1. Growth 1. Growth happens in part through the creation of new cells. 2. Replacement 1. These dead cells help protect us from infection and reduce the rate at which the underlying living cells dry out. 2. The cells living beneath the layers of dead cells are produced at a high rate by Mitosis. Page 232 Heat muscle cells and most neurons, in particular, do not seem to divide, or if they do divide, they do it very slowly. The rate at which Mitosis occurs in animals varies dramatically for different types of cells. Some cells die in a planned process of cell suicide called Apoptosis. This seemingly counterproductive strategy takes place in cells that are likely to accumulate significant genetic damage over time and are therefore at high risk of becoming cancer cells 8.6 Overview: mitosis leads to duplicate cells For Mitosis to begin, the parent cell replicates its DNA, creating a duplicate copy of

each chromosome. During Mitosis, newly duplicated chromosomes are separated into identical sets in 2 separate nuclei. After Mitosis, the cytoplasm and the rest of the cell are divided into 2 cells that pinch apart. Where once there was one parent cell, bow there are 2 identical daughter cells. Throughout the Cell Cycle except for Mitosis, chromosomes are uncoiled and spread out in a diffuse way. Just before Mitosis begins, 2 important events occur. 1. The chromosomes replicate, becoming 2 identical linear DNA molecules. 1. The 2 DNA molecules are held together at a region called the Centromere. 2. Throughout Mitosis, until the Centromeres separate, each of the identical DNA molecules is called a Chromatid. 3. Together the 2 are called Sister Chromatids. 2. The Sister Chromatids begin the process of Condensation, in which they coil tightly and become compact1. in contrast to the uncondensed and tangled state of the chromosomes prior to replication, during most of Interphase. Chromosomes are not X-shaped, they are linear. The X-shaped image is not simply a chromosome, but a Replicated chromosome Page 233 Because the sister chromatids need space to separate, the membrane around the nucleus is dismantled and disappears early in mitosis. At the same time, a structure called the Spindle is assembled. The Spindle is made mostly of hollow tubes of protein called Microtubules, which are part of the cell’s cytoskeleton. In animal cells, the threads originate and spread out at each pole from structured called Centrosomes, which contain a pair of Centrioles and a mass of proteins that anchor the Microtubules. These threads (known as Spindle Fibers) attach to the Centrosomes and pull the Sister Chromatids to the middle of the cell During Mitosis, they’ll eventually pull the Chromatids apart as cell division proceeds. Page 234 8.7 The details: Mitosis is a 4-stage process The ultimate result of Mitosis is the production of 2 cells with identical sets of chromosomes

Interphase: In Preparation for Mitosis, the Chromosomes Replicate During the DNA synthesis part of Interphase, Sister Chromatids are formed as every chromosome replicates itself. Each pair of Sister Chromatids is held together at the Centromere Mitosis The actual process of cell division occurs in 4 stages. 1 Prophase: Following replication, the Sister Chromatids condense Prophase begins when the Sister Chromatids condense. At this point, the Spindle forms and the nuclear envelope breaks down 2 Metaphase: The Chromatids congregate at the cell center After condensing, the pairs of Sister Chromatids seem to move aimlessly around the cell, but eventually they line up at the cell’s center, pulled by Spindle Fibers attached to a disk-like group of proteins, called a Kinetochore, that develops on the Centromeres. By the end of Metaphase, all the Chromatid pairs are lined up, straddling the center in a “single-file” congregation that is called the Metaphase Plate. The Chromatids are the most condensed during this part of Mitosis. 3 Anaphase: The Chromatids separate and move in opposite directions. In Anaphase, the Spindle Microtubules attached to the Centromeres begin pulling each of the Chromatids in a Sister Chromatid pair toward opposite poles of the cell. In each pair of Sister Chromatids, the Centromeres separate as one DNA molecule is pulled in one direction, and the other, identical DNA molecule, is pulled in the opposite direction. At the end of Anaphase, one full set of chromosomes is at one end of the cell, and another, identical full set is at the other end. Page 235 4 Telophase: New nuclear membranes form around the 2 complete chromosome sets With 2 full, identical sets of chromosomes collected at either end of the cell, the parent cell is prepared to divide into 2 genetically identical cells. In this last stage, the chromosomes begin to uncoil, fading from view, and nuclear membranes reassemble. The process of mitosis is generally accompanied by Cytokinesis, which typically begins during Telophase. During Cytokinesis, the cell’s cytoplasm is divided into approximately equal parts and the cell divides,

with some of the organelles going to each of the 2 new cells. When Cytokinesis is complete, the 2 new daughter cells, each with an identical nucleus containing identical genetic material, enter Interphase and begin the business of being cells. Page 236 8.8 Cell division out of control may result in cancer Cancer - Characterized by unrestrained cell growth and division that can damage adjacent tissues. Some cancers can Metastasize, or spread to other locations in the body. Cancer is the second leading cause of death in the US Only heart disease causes more deaths. Cancer occurs when some disruption of the DNA in a normal cell interferes with the cell’s ability to regulate cell division DNA disruption can be caused by chemical that mutate DNA, or by sources of high energy such as X rays. Whatever the cause, once a cell loses control over its cell cycle, cell division can proceed unrestrained. Cancer cells have several features that distinguish them from normal cells, the 3 most significant differences are the following: 1. Cancer cells lose their “contact inhibition” 1. Most normal cells divide until they touch other cells or collection of cells (tissues). 1. At that point, they stop dividing. 2. Cancer cells, however, ignore the signal that they are at high density and continue to divide. 2. Cancer cells can divide indefinitely. 1. Cancer cells, on the other hand, never lose their ability to divide and continue to do so indefinitely, even in the presence of conditions that would normally halt the cycle before cell division. 1. Cancer cells can divide indefinitely because they are able to rebuild their Telomeres following each cell division. 1. The normal cell Telomere can only divide 80-90 times. 3. Cancer cells have reduced “stickiness” 1. Cells are normally held together by adhesion molecules, proteins within cell membranes. 1. And cancer cells, too, usually group together, forming a tumor. 2. But the membranes of cancer cells tend to have reduced adhesiveness, causing them to stick to each other less than do non-cancerous cells. Page 237 Tumors caused by excessive cell growth and division are of 2 very different types: 1. Benign

2. Malignant Bening Tumors, such as moles, are just masses of normal cells that do not spread. Malignant Tumors, on the other hand, are the result of unrestrained growth of cancerous cells. Malignant Tumors shed and spread cancer cells, a process called Metastasis. Metastasis - In this process, cancer cells separate from a tumor and invade the circulatory system and lymphatic pathways, then spread to different parts of the body where they can cause the growth of additional tumors. How does cancer actually kill the organism? As a tumor gets larger, it uses up nutrients and energy, takes up more space, and presses against neighboring cells and tissues. Eventually, the tumor may block other cells and tissues from carrying out their normal functions and even kill them. To treat cancer, the rapidly dividing cells must be removed surgically or killed, or at least, their division slowed down. Currently, the killing and slowing down are done in 2 ways: 1. Chemotherapy 2. Radiation In Chemotherapy, drugs that interfere with cell division are administered, slowing down the growth of tumors. These drugs interfere with rapidly dividing cells through the entire body, not just the cancerous cells Like Chemotherapy, radiation works by disrupting cell division. Howev...