Chapter 11 Cell Division, Variations, Regulation and Cancer PDF

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Chapter 11: Cell Division, Variations, Regulation and Cancer ❖ Cell division is the process by which cells make more cells. ❖ The type of reproduction that occurs when offspring receive genetic material from a single parent is called asexual reproduction. ❖ Sexual reproduction results in offspring that receive genetic material from two parents. Half the genetic material is supplied by the female parent and is present in the egg and the other half is supplied by the male parent and is contributed by the male’s sperm. ➢ Eggs and sperm are specialized cells called gametes. ➢ A female gamete and a male gamete merge during fertilization to form a new organism. Gametes contain half the number of chromosomes as the other cells in the parent organism. 11.1 Cell Division ❖ The two daughter cells must each receive the full complement of genetic material (DNA) present in the single parent cell. ❖ The parent cell must be large enough to divide in two and still contribute sufficient cytoplasmic components such as proteins, lipids, and other macromolecules to each daughter cell. ❖ When eukaryotic cells divide, they first divide the nucleus by mitosis, and then divide the cytoplasm into two daughter cells by cytokinesis. ❖ Prokaryotic cells divide by binary fission. In this form of cell division, a cell replicates its DNA, increases in size, and divides into two daughter cells. Each daughter cell receives one copy of the replicated parental DNA. ➢ DNA replication is initiated at a specific location on the circular DNA molecule, called the origin of replication, and proceeds in opposite directions around the circle. ➢ The result is two DNA molecules, each of which is attached to the plasma membrane at a different site. The two attachment sites are initially close together. The cell then elongates and, as it does so, the two DNA attachment sites move apart. ➢ When the cell is about twice its original size and the DNA molecules are well separated, a constriction forms at the midpoint of the cell. Eventually, new

membrane and cell wall are synthesized at the site of the constriction, dividing the single cell into two. The result is two daughter cells, each having the same genetic material as the parent cell. ❖ The basic steps of binary fission—replication of DNA, segregation of replicated DNA to daughter cells, and division of one cell into two—occur in all forms of cell division. However, cell division in eukaryotes (by mitosis) is more complicated than cell division in prokaryotes (by binary fission). ❖ Eukaryotic cell division requires first the breakdown and then the re-formation of the nuclear envelope, as well as mechanisms other than cell growth to separate replicated DNA. ❖ Cell division in eukaryotic cells proceeds through a number of steps that make up the cell cycle. The cell cycle consists of two distinct stages: M phase and interphase. ➢ During M phase, the parent cell divides into two daughter cells. M phase consists of two different events: ■ Mitosis, the separation of the chromosomes into two nuclei. ■ Cytokinesis, the division of the cell itself into two separate cells. ➢ Interphase, is the time between two successive M phases. During this stage the cell makes many preparations for division. These preparations include replication of the DNA in the nucleus so that each daughter cell receives a copy of the genome, and an increase in cell size so that each daughter cell receives sufficient amounts of cytoplasmic and membrane components to allow it to survive on its own. ❖ Interphase can be divided into three phases. ➢ Since replication involves the synthesis of DNA, this stage is called S phase. ➢ In most cells, S phase does not immediately precede or follow mitosis but is separated from it by two gap phases: ■ G1 phase between the end of M phase and the start of S phase. ● During the G1 phase, specific regulatory proteins are made and activated. Once active, the regulatory proteins, many of which are kinases, then promote the activity of enzymes that synthesize DNA.

■ G2 phase between the end of S phase and the start of M phase. ● In the G2 phase, both the size and protein content of the cell increase in preparation for division. ❖ Many cells pause in the cell cycle somewhere between M phase and S phase. This period is called the G0 phase and is distinguished from G1 by the absence of preparations for DNA synthesis. 11.2 Mitotic Cell Division ❖ In eukaryotic cells, DNA is organized with histones and other proteins into chromatin, which can be looped and packaged to form the structures we know as chromosomes. One of the earliest events in mitosis is the condensing of chromosomes from long, thin, threadlike structures typical of interphase to short, dense forms that are identifiable under the microscope during M phase. ❖ When chromosomes condense and become visible during mitosis, they adopt characteristic shapes and sizes that allow each chromosome to be identified by its appearance in the microscope. The portrait formed by the number and shapes of chromosomes representative of a species is called its karyotype. ❖ In a normal human karyotype, the 46 chromosomes can be arranged into 23 pairs, 22 pairs of homologous chromosomes numbered 1 to 22 from the longest to the shortest chromosome and 1 pair of sex chromosomes. ❖ Each pair of homologous chromosomes represents two of the same type of chromosome (both carrying the same set of genes), one of which was received from the mother and the other from the father. ➢ The sex chromosomes are the X and Y chromosomes. Individuals with two X chromosomes are female, and those with an X and a Y chromosome are male. ❖ The number of complete sets of chromosomes in a cell is known as its ploidy. A cell with one complete set of chromosomes is haploid, and a cell with two complete sets of chromosomes is diploid. ❖ Even though the DNA in each chromosome duplicates, the two identical copies, called sister chromatids, do not separate. They stay side by side, physically held together at a constriction called the centromere.

❖ During mitosis, the sister chromatids separate from each other and go to opposite ends of the cell, so that each daughter cell receives the same number of chromosomes as present in the parent cell. ❖ Mitosis takes place in five stages. ❖ The first stage of mitosis is known as prophase and is characterized by the appearance of visible chromosomes. ❖ Outside the nucleus, in the cytosol, the cell begins to assemble the mitotic spindle, a structure made up predominantly of microtubules that pull the chromosomes into separate daughter cells. The centrosome is a compact structure that is the microtubule organizing center for animal cells. ❖ As part of the preparation for mitosis during S phase in animal cells, the centrosome duplicates and each one begins to migrate around the nucleus, the two ultimately halting at opposite poles in the cell at the start of prophase. ❖ The final locations of the centrosomes define the opposite ends of the cell that will eventually be separated into two daughter cells. As the centrosomes make their way to the poles of the cell, tubulin dimers assemble around them, forming microtubules that radiate from each centrosome. These radiating filaments form the mitotic spindle and later serve as the guide wires for chromosome movement. ❖ In the next stage of mitosis, known as prometaphase, the nuclear envelope breaks down and the microtubules of the mitotic spindle attach to chromosomes. The microtubules radiating from the centrosomes grow and shrink as they explore the region of the cell where the nucleus once was. ❖ As the ends of the microtubules encounter chromosomes, they attach to the chromosomes at their centromeres. Associated with the centromere of each chromosome are two protein complexes called kinetochores, one located on each side of the constriction. ❖ Each kinetochore is associated with one of the two sister chromatids and forms the site of attachment for a single spindle microtubule. This arrangement ensures that each sister chromatid is attached to a spindle microtubule radiating from one of the poles of the cell. The symmetrical tethering of each chromosome to the two poles of the cell is essential for proper chromosome segregation.

❖ Once each chromosome is attached to the mitotic spindles from both poles of the cell, the microtubules of the mitotic spindle lengthen or shorten to move the chromosomes into position in the middle of the cell. There the chromosomes are lined up in a single plane that is roughly equidistant from both poles of the cell. ❖ This stage of mitosis, when the chromosomes are aligned in the middle of the dividing cell, is called metaphase. ❖ In the next stage of mitosis, called anaphase, the sister chromatids separate. The centromere holding a pair of sister chromatids together splits, allowing the two sister chromatids to separate from each other. After separation, each chromatid is considered to be a full-fledged chromosome. The spindle microtubules attached to the kinetochores gradually shorten, pulling the newly separated chromosomes to the opposite poles of the cell. ❖ Once a complete set of chromosomes arrives at a pole, the chromosomes have entered the area that will form the cytosol of a new daughter cell. This event marks the beginning of telophase, during which the cell prepares for its division into two new cells. The microtubules of the mitotic spindle break down and disappear, while a nuclear envelope reforms around each set of chromosomes, creating two new nuclei. As the nuclei become increasingly distinct in the cell, the chromosomes contained within them decondense, becoming less visible in the microscope. This stage marks the end of mitosis. ❖ Usually, as mitosis is nearing its end, cytokinesis begins and the parent cell divides into two daughter cells. In animal cells, this stage begins when a ring of actin filaments, called the contractile ring, forms against the inner face of the cell membrane at the equator of the cell perpendicular to the axis of what was the spindle. ❖ The ring contracts, pinching the cytoplasm of the cell and dividing it in two. The constriction of the contractile ring is driven by motor proteins that slide bundles of actin filaments in opposite directions. Successful division results in two daughter cells, each with its own nucleus. The daughter cells are now free to enter G1 phase and start the process again.

❖ For the most part, mitosis is similar in animal and in plant cells, but cytokinesis is different. Since plant cells have a cell wall, the division of the cell is achieved by constructing a new cell wall. ➢ During telophase, dividing plant cells form a structure called the phragmoplast in the middle of the cell. The phragmoplast consists of overlapping microtubules that guide vesicles containing cell wall components to the middle of the cell. During late anaphase and telophase, these vesicles fuse to form a new cell wall, called the cell plate, in the middle of the dividing cell. Once this developing cell wall is large enough, it fuses with the original cell wall at the perimeter of the cell. Cytokinesis is then complete and the plant cell has divided into two daughter cells. 11.3 Meiotic Cell Division ❖ Gametes are produced by meiotic cell division, a form of cell division that includes two rounds of nuclear division. By producing haploid gametes, meiotic cell division makes sexual reproduction possible. ❖ Meiotic cell division results in four daughter cells instead of two. Each of the four daughter cells contains half the number of chromosomes as the parent cell. The four daughter cells are each genetically unique. ❖ Meiotic cell division consists of two successive cell divisions. The two cell divisions are called meiosis I and meiosis II, and they occur one after the other. Each cell division results in two cells, so that by the end of meiotic cell division a single parent cell has produced four daughter cells. ➢ During meiosis I, homologous chromosomes separate from each other, reducing the total number of chromosomes by half. During meiosis II, sister chromatids separate. ❖ Meiosis I begins with prophase I. The chromosomes first appear as long, thin threads present throughout the nucleus. By this time, DNA replication has already taken place, so each chromosome has become two sister chromatids held together at the centromere. ❖ The homologous chromosomes pair with each other, coming together to lie side by side, gene for gene, in a process known as synapsis.

❖ Because each homologous chromosome is a pair of sister chromatids attached to a single centromere, a pair of synapsed chromosomes creates a four-stranded structure: two pairs of sister chromatids aligned along their length. The whole unit is called a bivalent, and the chromatids attached to different centromeres are called non-sister chromatids. ❖ Non-sister chromatids result from the replication of homologous chromosomes (one is maternal and the other is paternal in origin), so they have the same set of genes in the same order, but are not genetically identical. By contrast, sister chromatids result from replication of a single chromosome, so are genetically identical. ❖ Within the bivalents are cross-like structures, each called a chiasma. Each chiasma is a visible manifestation of a crossover, the physical breakage and reunion between nonsister chromatids. ❖ Through the process of crossing over, homologous chromosomes of maternal origin and paternal origin exchange DNA segments. The positions of these exchanges along the chromosome are essentially random, and therefore each chromosome that emerges from meiosis is unique, containing some DNA segments from the maternal chromosome and others from the paternal chromosome. ❖ The number of chiasmata that are formed during meiosis depends on the species. ❖ At the end of prophase I, the chromosomes are fully condensed and have formed chiasmata, the nuclear envelope has begun to disappear, and the meiotic spindle is forming. ❖ In prometaphase I, the nuclear envelope breaks down and the meiotic spindles attach to kinetochores on chromosomes. In metaphase I, the bivalents move so that they come to lie on an imaginary plane cutting transversely across the spindle. Each bivalent lines up so that its two centromeres lie on opposite sides of this plane, pointing toward opposite poles of the cell. Importantly, the orientation of these bivalents is random with respect to each other. The random alignment of chromosomes on the spindle in metaphase I further increases genetic diversity in the products of meiosis. ❖ At the beginning of anaphase I, the two homologous chromosomes of each bivalent separate as they are pulled in opposite directions. The key feature of anaphase I is that the centromeres do not split and the two chromatids that make up each chromosome remain together.

❖ The end of anaphase I coincides with the arrival of the chromosomes at the poles of the cell. Only one of the two homologous chromosomes goes to each pole. Meiosis I is sometimes called the reductional division since it reduces the number of chromosomes in daughter cells by half. ❖ In telophase I, the chromosomes may uncoil slightly and a nuclear envelope briefly reappears. ❖ In meiosis II, sister chromatids separate, creating haploid daughter cells. Starting with prophase II, the second meiotic division is in many respects like a normal mitotic division, except that the nuclei in prophase II have the haploid number of chromosomes, not the diploid number. In prophase II, the chromosomes recondense to their maximum extent. Toward the end of prophase II, the nuclear envelope begins to disappear (in those species in which it has formed), and the spindle begins to be set up. ❖ In prometaphase II, spindles attach to kinetochores and, in metaphase II, the chromosomes line up so that their centromeres lie on an imaginary plane cutting across the spindle. ❖ In anaphase II, the centromere of each chromosome splits. The separated chromatids, now each regarded as a full-fledged chromosome, are pulled toward opposite poles of the spindle. In this sense, anaphase II resembles anaphase of mitosis. ❖ Finally, in telophase II, the chromosomes uncoil and become decondensed and a nuclear envelope re-forms around each set of chromosomes. The nucleus of each cell resulting from telophase II has the haploid number of chromosomes. Because cells in meiosis II have the same number of chromosomes at the beginning and at the end of the process, meiosis II is often called the equational division. Telophase II is followed by the division of the cytoplasm in many species.

❖ In multicellular organisms, division of the cytoplasm in meiotic cell division differs between the sexes. ➢ In female mammals, the cytoplasm is divided very unequally in both meiotic divisions. Most of the cytoplasm is retained in one meiotic product, a very large cell called the oocyte, which can develop into the functional egg cell, and the other meiotic products receive only small amounts of cytoplasm. These smaller cells are called polar bodies. ➢ In male mammals, the cytoplasm divides about equally in both meiotic divisions, and each of the resulting meiotic products goes on to form a functional sperm. During the development of the sperm, most of the cytoplasm is eliminated, and what is left is essentially a nucleus in the sperm head equipped with a long whiplike flagellum to help propel it toward the egg. ❖ Sexual reproduction involves two processes: meiotic cell division and fertilization. Meiotic cell division, produces cells with half the number of chromosomes present in

the parent cell. In multicellular animals, the products of meiotic cell division are gametes: An egg cell is a gamete and a sperm cell is a gamete. Each gamete is haploid, containing a single set of chromosomes. ❖ During fertilization, these gametes fuse to form a single cell called a zygote. The zygote is diploid, having two complete sets of chromosomes, one from each parent. Therefore, fertilization restores the original chromosome number. 11.4 Regulation of the Cell Cycle ❖ Both mitotic and meiotic cell division must occur only at certain times and places. Mitotic cell division, occurs during growth of a multicellular organism, wound healing, or in the maintenance of actively dividing tissues such as the skin or lining of the intestine. ❖ Meiotic cell division occurs only at certain times during development. ❖ Even when a cell receives a signal to divide, it does not divide until it is ready. ❖ Cells have regulatory mechanisms that initiate cell division, as well as mechanisms for spotting faulty or incomplete preparations and arresting cell division. ❖ During rapid cell divisions, mitosis and S phase alternate with virtually no G1and G2 phases in between. As the cells undergo this rapid series of divisions, several proteins appear and disappear in a cyclical fashion. Researchers interpreted this observation to mean that these proteins might play a role in the control of the progression through the cell cycle. Second, several enzymes become active and inactive in cycles. These enzymes are kinases, proteins that phosphorylate other proteins. ❖ Proteins are synthesized that activate the kinases. These regulatory proteins are called cyclins because their levels rise and fall with each turn of the cell cycle. Once activated by cyclins, the kinases phosphorylate target proteins involved in promoting cell division. These kinases, cyclin-dependent kinases, are always present within the cell but are active only when bound to the appropriate cyclin. It is the kinase activity of the cyclin– CDK complexes that triggers the required cell cycle events. ❖ In mammals, there are several different cyclins and CDKs that act at specific steps of the cell cycle.

❖ The G1/S cyclin–CDK complex, which is active at the end of the G1 phase, is necessary for the cell to enter S phase. ❖ The S cyclin–CDK complex is necessary for the cell to initiate DNA synthesis. It activates enzymes and other proteins necessary for DNA replication. Once replication has begun at a particular place on the DNA, S cyclin–CDK activity prevents the replication proteins from reassembling at the same place and re-replicating the same DNA sequence. ❖ The ...