Written Assignment 2

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Just as a car comes with an odometer, which keeps track of how far a vehicle has been driven, animal cells have a mechanism that keeps track of how many times the cell has divided. It’s a section of DNA, called the “telomere,” at the tip of every chromosome. Every time a cell divides, the telomere gets a bit shorter. Occurring right next to the valuable DNA sequences that specify genes, the telomere is like a protective cap at the end of the DNA. But after a critical number of cell divisions, with the telomere getting shorter and shorter each time, any additional cell divisions will cause the loss of functional, essential DNA, which means almost certain death for the cell (Figure 8-1). Every time a cell divides, making an exact copy of itself, its DNA divides as well. However, each time the DNA divides, the process by which chromosomes are duplicated causes the telomere at each end of every chromosome to get a bit shorter. At birth, the telomeres in most human cells are long enough to support 80–90 cell divisions. In a 70-year-old person, the telomeres are only long enough for about 20–30 divisions. 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.

Occasionally, individuals are born with telomeres that impair the functioning of a protein that helps maintain the nucleus of cells. This genetic condition, called Hutchinson-Gilford progeria syndrome, causes the cell’s telomeres to be much shorter than normal. In addition, the normal functioning of many genes is disrupted, and consequently, cells and tissues begin to appear aged very soon after birth. Children with this disorder rarely live beyond the age of 13. Given this information, you might wonder if, by rebuilding the telomere after each round of division, the cell and its descendants could function for a longer time than normal. Such a line of cells would never die. By extension, it’s tempting to imagine that constantly rebuilding telomeres might act like a fountain of youth. Unfortunately, it does not. Some cells do rebuild their telomeres after each cell division, restoring the chromosomes’ protective caps. For single-celled eukaryotic organisms and for the cells that divide to produce sperm and eggs in multicellular organisms (cells that must go through many thousands of rounds of cell division), this telomere rebuilding is essential. 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. Because telomere rebuilding occurs in (and possibly is necessary to) many human cancers, researchers have hopes that inhibiting it might help fight cancer. In any case, because one of the defining features of cancer is runaway cell division, discovering a cure for cancer will necessarily involve a deep understanding of how cells divide.

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All life on earth uses DNA to store genetic information. This fact is remarkable considering the

tremendous diversity of life on our planet—from single-celled bacteria to multicellular plants

and animals. One way in which the DNA of different species varies is in how it is organized into

chromosomes.

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.

But eukaryotic chromosomes (and some prokaryotic chromosomes) are made of more than

just DNA. 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. Plants and animals

usually have between 10 and 50 chromosomes (although there are species with as few as 2

and others with more than 100).

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Most prokaryotes—the bacteria and archaea—have less DNA than eukaryotes. They carry their genetic information in a single, circular chromosome, a closed 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” (Figure 8- 4). This process begins with 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 two separated, single- stranded, circular molecules of DNA. As the double-stranded molecule unzips, enzymes bind to the DNA and attach free-floating nucleotides to the growing DNA backbone, matching A to T and G to C, thus creating two identical double-stranded DNA molecules. The two newly created circular chromosomes attach to the inside of the plasma membrane, each at a different spot. The original cell, called the parent cell, then pinches in somewhere between these two spots until it divides into two new cells, called daughter cells. Each of the daughter cells has an identical two-stranded copy of the original two-stranded circular chromosome. In some prokaryotes, such as the bacteria called E. coli that live in our digestive system, the complete process of binary fission can occur very quickly—often in as little as 20 minutes. 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.

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Most eukaryotic cells go through phases—they spend long periods of time occupied with activities relating solely to their growth, and then may suspend those activities as they segue into a period devoted exclusively to reproducing themselves. This alternation of activities between processes related to growth and processes related to cell division is called the cell cycle. All the cells of a multicellular eukaryotic organism can be divided into two types: somatic cells are the cells forming the body of the organism; reproductive cells are the sex cells—the gametes (sperm and eggs) and the cells that give rise to them. Somatic cells and reproductive cells use different methods of producing new cells. The two main phases in the cell cycle are interphase, during which the cell grows and prepares to divide, and the mitotic phase (or M phase), during which division occurs. Interphase is further divided into three distinct sub-phases, described on subsequent slides. 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, and so on). Most cells inhabit the Gap 1 phase the majority of the time. However, some cells enter a state called G0, which is a “resting” phase outside the cell cycle in which no cell division occurs. Gap 2 (G2). Significant growth occurs in this phase, along with high rates of protein synthesis in preparation for division. Mitotic Phase This period begins with mitosis, a process in which the parent cell’s nucleus, including its chromosomes, divides. Mitosis is generally followed by cytokinesis (which may begin before the end of mitosis), during which the cytoplasm is divided into two daughter cells.

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Variation in the rates of cell division is regulated by a 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, 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. Checkpoints in the cell cycle make it possible for cells to (a) reduce the likelihood of completing cell division when errors have occurred in the process, and (b) respond to feedback conveying information about the cell’s internal and external environment. The signals that trigger transitions to subsequent phases in the cell cycle most commonly consist of growth factors, which provide feedback about the cell’s environment and can signal that division is appropriate. There are three primary checkpoints that regulate the cell cycle in eukaryotes. 1. G1/S checkpoint: assessing DNA damage and cell growth. 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. 2. G2/M checkpoint: assessing DNA synthesis. Just before beginning mitosis, a cell reaches the G2/M checkpoint. This checkpoint serves as a “mitosis readiness” assessment. 3. Spindle assembly checkpoint: assessing anaphase readiness during mitosis. This important cell-cycle checkpoint occurs during mitosis. 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. If this checkpoint is passed, the cell completes cell division.

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In one of the great understatements in the scientific literature, James Watson and Francis Crick, in their paper describing the structure of DNA, wrote: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” Watson and Crick were referring to the feature of DNA called 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 two DNA molecules—each identical to the original DNA molecule—one for each of the two new cells (Figure 8-7).

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Recall from Chapter 6 that the individual units that make up DNA are nucleotides, which have three components: a nitrogen-containing molecule called a base, a phosphate group, and a molecule of a five-carbon sugar. Each of the five carbon atoms in the sugar molecules is given a number. The nitrogenous base is attached to the 1′ (pronounced “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.

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The process of DNA replication occurs in two steps: (1) unwinding and separation of the two strands, and (2) reconstruction and elongation of new complementary strands. A feature of DNA that has important consequences for the process of replication is that its two strands run in opposite directions. (1) Unwinding and separation. Replication begins at a specific site, called the origin of

replication, where the coiled, double-stranded DNA molecule unwinds and separates into two 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 two complementary strands. The unwinding and separating of the two DNA strands creates what is called a replication fork.

(2) Reconstruction and elongation. At the replication fork, a group of several proteins, called a replication complex, binds to each of the exposed strands. This complex includes the enzyme DNA polymerase, which 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.

DNA replication occurs in all types of cells, somatic and reproductive, before cell division. The result of replication is two double-stranded DNA molecules that carry virtually the same genetic information. This makes it possible for the somatic cells of the body that are produced by cell division to have a virtually identical genetic composition. Note, though, that the daughter DNA molecules are not completely identical. Replication is accompanied by a very low rate of errors—about one error per several billion base pairs in eukaryotes.

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A variety of mutations (such as mismatched bases and added or deleted segments) can occur during replication (or when DNA is damaged by some external source, such as X rays). 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. Not all errors are corrected, however. And if an error remains, the sequences in a replicated DNA molecule (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. When an error is introduced into the DNA of a gamete-producing cell (i.e., one that divides to make sperm or eggs), a new gene can sometimes enter a population in the next generation and be acted on by evolution. We explore the relationship between mutation and evolution in more detail in Chapter 10.

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