Written Assignment 2

What is dust? It is primarily dead skin cells. You (and your friends and family) slough off millions of dead skin cells each day—yet your skin doesn’t disappear because your body replaces the sloughed-off cells through the process of mitosis. Mitosis has just one purpose: to enable existing cells to generate new, genetically identical cells. Mitosis is required for growth and replacement.

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Every day, a huge number of cells in an organism must be replaced by mitosis. In humans, this number is in the billions. Nearly all the somatic cells of the body—that is, all cells except sperm- and egg-producing cells—undergo mitosis. There are a few notable exceptions, as we’ve already seen. Heart muscle cells and most neurons, in particular, do not seem to divide, or, if they do divide, they do it very slowly. (We don’t know why this is so.) The rate at which mitosis occurs in animals varies dramatically for different types of cells. The most rapid cell division takes place in the bone marrow as red blood cells are produced, as well as in the cells lining various tissues and organs. The average red blood cell, for example, circulates for two to four months and then must be replaced. The cells lining the intestines are replaced about every three weeks. Hair follicles, too, contain some of the most rapidly dividing 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 (a process described later in this chapter). Cells targeted for apoptosis include many of the cells lining the digestive tract and cells in the liver, two locations where cells are almost constantly in contact with harmful substances.

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Throughout the cell cycle except for mitosis, chromosomes are uncoiled and spread out in a diffuse way, like a mass of spaghetti. And because they are so stretched out, they are not dense enough to be visible under a light microscope. However, just before mitosis begins, two important events occur. 1. The chromosomes replicate, becoming two identical linear DNA molecules. The two DNA molecules are held together at a region (on each molecule) called the centromere. Throughout mitosis, until the centromeres separate, each of the identical DNA molecules is called a chromatid; together, the two are called sister chromatids (Figure 8-13). 2. The sister chromatids begin the process of condensation, in which they coil tightly and become compact—in contrast to the uncondensed and tangled state of the chromosomes prior to replication, during most of interphase. When the sister chromatids condense, they look like the letter X. Nevertheless, chromosomes are not X-shaped. They are linear. The reason the genetic material appears as X-shaped chromosomes in most photos is that once it has condensed in preparation for cell division, it is coiled tightly and only then is thick enough to be seen and photographed under the light microscope. And so the X-shaped image is not simply a chromosome, but a replicated chromosome. 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. They resemble a group of threads stretching across the cell between its two ends, or poles. In animal cells, the threads originate and spread out at each pole from structures 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 centromeres and pull the sister chromatids to the middle of the cell. During mitosis, they’ll eventually pull the chromatids apart as cell division proceeds.

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For mitosis to begin, the parent cell replicates its DNA, creating a duplicate copy of each chromosome. Once this task is completed, mitosis can take place. Mitosis occurs in just four steps, in which the now-duplicated chromosomes are separated into identical sets in two separate nuclei, after which the cytoplasm and the rest of the cell are divided into two cells that pinch apart. Where once there was one parent cell, now there are two identical daughter cells.

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Interphase: In Preparation for Mitosis, the Chromosomes Replicate. Processes essential to cell division take place even before the mitotic phase of the cell cycle begins. 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 four stages (Figure 8-14). 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 line up at the cell’s center, pulled by spindle fibers attached to a disk-like group of proteins that develops on the centromeres. By the end of metaphase, all the chromatid pairs are lined up in an orderly fashion, straddling the center in a single-file congregation called the meta-phase plate. The chromatids are at their most condensed during this part of mitosis.

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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. 4. Telophase: new nuclear membranes form around the two complete chromosome sets. With two full, identical sets of chromosomes collected at either end of the cell, the parent cell is prepared to divide into two genetically identical cells. In this last stage, called telophase, 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 two new cells. When cytokinesis is complete, the two new daughter cells enter interphase and begin the business of being cells.

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Cell growth and division are necessary to the health of most organisms. But too much of a good thing can be bad. Cancer is 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 can cause serious health problems and is the second leading cause of death in the United States, responsible for more than 20% of all deaths. 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 chemicals that mutate DNA or by sources of high energy such as X rays, the sun, or nuclear radiation. Cancer can even be caused by some viruses. Whatever the cause, once a cell loses control over its cell cycle, cell division can proceed unrestrained.

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Cancer cells have several features that distinguish them from normal cells. 1. Cancer cells lose their contact inhibition. Most normal cells divide until they touch other cells or collections of cells (tissues). At that point, they stop dividing. Cancer cells, however, ignore the signal that they are at high density and continue to divide. 2. Cancer cells can divide indefinitely. As we saw in Section 8-1, most normal human cells can divide 80–90 times. After that point, a cell may continue living but it loses the ability to divide. 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 cell cycle before cell division. (Cancer cells can divide indefinitely because they are able to rebuild their telomeres following each cell division, as we saw in Section 8-1.) 3. Cancer cells have reduced “stickiness.” Cells are normally held together by adhesion molecules, proteins within cell membranes. And cancer cells, too, usually group together, forming a tumor. But the membranes of cancer cells tend to have reduced adhesiveness, causing them to stick to each other less than do non-cancerous cells.

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Tumors caused by excessive cell growth and division are of two very different types: benign and malignant. Benign tumors, such as many moles, are just masses of normal cells that do not spread. They can usually be removed safely without any lasting consequences. Malignant tumors, on the other hand, are the result of unrestrained growth of cancerous cells (Figure 8- 16). Malignant tumors shed and spread cancer cells, a process called 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? Somewhat surprisingly, it’s not because of some toxic action of the cancer cells themselves. As a tumor gets larger, it uses up nutrients and energy, takes up more and 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. This cell dysfunction or cell death can have disastrous consequences when the job of the affected normal tissue is to control critical processes such as breathing, heart function, or the detoxification processes in the liver.

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To treat cancer, the rapidly dividing cells must be removed surgically or killed, or their division at least slowed down. Currently, the killing and slowing down are done in two ways: by chemotherapy and by radiation. In chemotherapy, drugs that interfere with cell division are administered, slowing down the growth of tumors. Because these drugs interfere with rapidly dividing cells throughout the body (not just the rapidly dividing cancer cells), they can have very unpleasant side effects. In particular, chemotherapy drugs disrupt normal systems that rely on the rapid and constant production of new cells. For instance, chemotherapy often causes extreme fatigue and shortness of breath because it reduces the rate at which red blood cells are produced, thus limiting the amount of oxygen that can be transported throughout the body. Like chemotherapy, radiation works by disrupting cell division. Unlike the drugs used in chemotherapy, however, which circulate throughout the entire body, radiation therapy directs high-energy radiation only at the part of the body where a tumor is located. As with chemotherapy, the radiation process is not perfect, and nearby tissue is often harmed. The patients may be asymptomatic at the time of treatment. What causes cancer? Researchers have made significant progress toward understanding cancer at the cellular level. Most cancer is caused by mutations in a cell’s DNA that disrupt the normal processes that control and regulate the cell cycle. More specifically, the cancer-causing mutations seem to affect two different types of genes: those that stimulate cell growth and those that restrain it. Although there is no complete cure for cancer, many potentially successful therapies for treatment and prevention are on the horizon. Extensive research is being conducted on the mechanisms by which genes controlling the cell cycle are damaged in cancer cells, for example, and how such damage might be prevented or reversed.

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