《生物学》课程参考书籍文献（英文版，Chapter 11 - Chapter 19）Part IV Reproduction and Heredity、Part V Molecular Genetics

Controlling the Cell Cycle in factors to be identified: platelet-derived growth factor Multicellular Eukaryotes (PDGF. When PdgF binds to a membrane receptor, it The cells of multicellular eukaryotes are not free to make initiates an amplifying chain of internal cell signals that individual decisions about cell division, as yeast cells are. stimulates cell division. pdgf was discovered when inves- tigators found that fibroblasts would grow and divide in tis- The body s organization cannot be maintained without se- sue culture only if the growth medium contained blood divide, and only at appropriate times. The way that cells in serum(the liquid that remains after blood clots); blood hibit individual growth of other cells is apparent in mam- plasma(blood from which the cells have been removed without clotting) would not work. The researchers hypoth malian cells growing in tissue culture: a single layer of cells esized that platelets in the blood clots were releasing into expands over a culture plate until the growing border of the serum one or more factors required for fibroblast cells comes into contact with neighboring cells, and then growth. Eventually, they isolated such a factor and named the cells stop dividing. If a sector of cells is cleared away boring cells rapidly refill that sector and then stop di it Pdgf. growth factors such as pdgf override cellular again. How are cells able to sense the density of the controls that otherwise inhibit cell division when a tissue cell culture around them? Each growing cell apparently Is injured, a blood clot forms and the release of PDGF trig- binds minute amounts of positive regulatory signals called gers neighboring cells to divide helping to heal the wound owth factors, proteins that stimulate cell division(such Only a tiny amount of PDGF (approximately 10-10 M)is as MPF). When neighboring cells have used up what little required to stimulate cell division growth factor is present, not enough is left to trigger cell Characteristics of Growth Factors. Over 50 different proteins that function as growth factors have been isolated (table 11.2 lists a few), and more undoubtedly exist. A spe- Growth Factors and the Cell Cycle cific cell surface receptor"recognizes"each growth factor, its shape fitting that growth factor precisely. When the As you may recall from chapter 7(cell-cell interactions), growth factor binds with its receptor, the receptor reacts by growth factors work by triggering intracellular signaling triggering events within the cell(figure 11. 19). The cellular systems. Fibroblasts, for example, possess numerous recep selectivity of a particular growth factor depends upon tors on their plasma membranes for one of the first growth which target cells bear its unique receptor. Some growth Table 11.2 growth Factors of mammalian Cells Growth y Effect Epidermal growth Broad Stimulates cell proliferation in many tissues; plays a key role in factor (EGF gulating embryonic development Narrow Required for proliferation of red blood cell precursors and their Fibroblast growth Broad Initiates the proliferation of many cell types; inhibits maturation factor ( FGF of many types of stem cells; acts as a signal in embryonic Insulin-like Stimulates metabolism of many cell types; potentiates the effects owth factor of other growth factors in promoting cell proliferation Narrow Triggers the division of activated T lymphocytes during the immune response factor (MPF) ung Broad Regulates entrance of the cell cycle into the M phase Nerve growth arrow Stimulates the growth of neuron processes during neural factor NGE development Platelet-derived growth Broad Promotes the proliferation of many connective tissues and some factor(PDGF neuroglial cells Accentuates or inhibits the responses of many cell types to other factor B(TGF-B) growth factors; often plays an important role in cell differentiation 220 Part IV Reproduction and Heredity

Controlling the Cell Cycle in Multicellular Eukaryotes The cells of multicellular eukaryotes are not free to make individual decisions about cell division, as yeast cells are. The body’s organization cannot be maintained without se￾verely limiting cell proliferation, so that only certain cells divide, and only at appropriate times. The way that cells in￾hibit individual growth of other cells is apparent in mam￾malian cells growing in tissue culture: a single layer of cells expands over a culture plate until the growing border of cells comes into contact with neighboring cells, and then the cells stop dividing. If a sector of cells is cleared away, neighboring cells rapidly refill that sector and then stop di￾viding again. How are cells able to sense the density of the cell culture around them? Each growing cell apparently binds minute amounts of positive regulatory signals called growth factors, proteins that stimulate cell division (such as MPF). When neighboring cells have used up what little growth factor is present, not enough is left to trigger cell division in any one cell. Growth Factors and the Cell Cycle As you may recall from chapter 7 (cell-cell interactions), growth factors work by triggering intracellular signaling systems. Fibroblasts, for example, possess numerous recep￾tors on their plasma membranes for one of the first growth factors to be identified: platelet-derived growth factor (PDGF). When PDGF binds to a membrane receptor, it initiates an amplifying chain of internal cell signals that stimulates cell division. PDGF was discovered when inves￾tigators found that fibroblasts would grow and divide in tis￾sue culture only if the growth medium contained blood serum (the liquid that remains after blood clots); blood plasma (blood from which the cells have been removed without clotting) would not work. The researchers hypoth￾esized that platelets in the blood clots were releasing into the serum one or more factors required for fibroblast growth. Eventually, they isolated such a factor and named it PDGF. Growth factors such as PDGF override cellular controls that otherwise inhibit cell division. When a tissue is injured, a blood clot forms and the release of PDGF trig￾gers neighboring cells to divide, helping to heal the wound. Only a tiny amount of PDGF (approximately 10–10 M) is required to stimulate cell division. Characteristics of Growth Factors. Over 50 different proteins that function as growth factors have been isolated (table 11.2 lists a few), and more undoubtedly exist. A spe￾cific cell surface receptor “recognizes” each growth factor, its shape fitting that growth factor precisely. When the growth factor binds with its receptor, the receptor reacts by triggering events within the cell (figure 11.19). The cellular selectivity of a particular growth factor depends upon which target cells bear its unique receptor. Some growth 220 Part IV Reproduction and Heredity Table 11.2 Growth Factors of Mammalian Cells Growth Range of Factor Specificity Effects Epidermal growth factor (EGF) Erythropoietin Fibroblast growth factor (FGF) Insulin-like growth factor Interleukin-2 Mitosis-promoting factor (MPF) Nerve growth factor (NGF) Platelet-derived growth factor (PDGF) Transforming growth factor β (TGF-) Broad Narrow Broad Broad Narrow Broad Narrow Broad Broad Stimulates cell proliferation in many tissues; plays a key role in regulating embryonic development Required for proliferation of red blood cell precursors and their maturation into erythrocytes (red blood cells) Initiates the proliferation of many cell types; inhibits maturation of many types of stem cells; acts as a signal in embryonic development Stimulates metabolism of many cell types; potentiates the effects of other growth factors in promoting cell proliferation Triggers the division of activated T lymphocytes during the immune response Regulates entrance of the cell cycle into the M phase Stimulates the growth of neuron processes during neural development Promotes the proliferation of many connective tissues and some neuroglial cells Accentuates or inhibits the responses of many cell types to other growth factors; often plays an important role in cell differentiation

Growth factor Nuclear membrane Cell surface Chromosome Cytoplasm Nucleus FIGURE 11.19 The cell proliferation-signaling pathway. Binding of a growth factor sets in motion a cascading intracellular signaling pathway (described in chapter 7), which activates nuclear regulatory proteins that trigger cell division. In this example, when the nuclear protein rb is phosphorylated, another nuclear protein(myc) is released and is then able to stimulate the production of Cdk proteins factors, like PDGF and epidermal growth factor(EGF), af- It is the ability to enter go that accounts for the in fect a broad range of cell types, while others affect only credible diversity seen in the length of the cell cycle specific types. For example, nerve growth factor (NGF among different tissues. Epithelial cells lining the gut di- promotes the growth of certain classes of neurons, and ery- vide more than twice a da y, constantly renewing the lin sors. Most animal cells need a combination of several dif- only once every year or two, spending most of their vide ferent growth factors to overcome the various controls that in Go phase. Mature neurons and muscle cells usually inhibit cell division never leave go. The Go Phase. If cells are deprived of appropriate growth factors, they stop at the gi checkpoint of the cell cycle. With their growth and division arrested, they remain Two groups of proteins, cyclins and Cdks, interact to regulate the cell cycle. Cells also receive protein signals in the Go phase, as we discussed earlier. This nongrowing called growth factors that affect cell division. state is distinct from the interphase stages of the cell cycle, GI S, and g Chapter 11 How Cells Divide 221

factors, like PDGF and epidermal growth factor (EGF), af￾fect a broad range of cell types, while others affect only specific types. For example, nerve growth factor (NGF) promotes the growth of certain classes of neurons, and ery￾thropoietin triggers cell division in red blood cell precur￾sors. Most animal cells need a combination of several dif￾ferent growth factors to overcome the various controls that inhibit cell division. The G0 Phase. If cells are deprived of appropriate growth factors, they stop at the G1 checkpoint of the cell cycle. With their growth and division arrested, they remain in the G0 phase, as we discussed earlier. This nongrowing state is distinct from the interphase stages of the cell cycle, G1, S, and G2. It is the ability to enter G0 that accounts for the in￾credible diversity seen in the length of the cell cycle among different tissues. Epithelial cells lining the gut di￾vide more than twice a day, constantly renewing the lin￾ing of the digestive tract. By contrast, liver cells divide only once every year or two, spending most of their time in G0 phase. Mature neurons and muscle cells usually never leave G0. Two groups of proteins, cyclins and Cdks, interact to regulate the cell cycle. Cells also receive protein signals called growth factors that affect cell division. Chapter 11 How Cells Divide 221 Cytoplasm Nucleus Cell division Nuclear membrane Growth factor Protein kinase cascade myc Rb Nuclear pores Rb myc Chromosome Cdk Cell surface receptor P P P P P FIGURE 11.19 The cell proliferation-signaling pathway. Binding of a growth factor sets in motion a cascading intracellular signaling pathway (described in chapter 7), which activates nuclear regulatory proteins that trigger cell division. In this example, when the nuclear protein Rb is phosphorylated, another nuclear protein (myc) is released and is then able to stimulate the production of Cdk proteins

Cancer and the Control of Cell (cell suicide)program(see chapter 17 for a discussion of Proliferation By halting division in damaged cells, p53 preve ents the The unrestrained, uncontrolled growth of cells, called development of many mutated cells, and it is therefore con- cancer, is addressed more fully in chapter 18. However, sidered a tumor-suppressor gene(even though its activities ncer certainly deserves mention in a chapter on cell di- are not limited to cancer prevention). Scientists have found vision, as it is essentially a disease of cell division-a fail- that p53 is entirely absent or damaged beyond use in the ure of cell division control. Recent work has identified one majority of cancerous cells they have examined! It is pre- have repeatedly identified what has proven to be the same are able to repeatedly undergo cell division without being ne! Officially dubbed p53(researchers italicize the gene halted at the Gi checkpoint(figure 11. 20) symbol to differentiate it from the protein), this gene entists administered healthy p53 protein to rapidly dividing plays a key role in the Gi checkpoint of cell division. The cancer cells in a petri dish: the cells soon ceased dividing rene's product, the p53 protein, monitors the integrity of and died DNA, checking that it is undamaged. If the p53 protein Scientists at Johns Hopkins University School of Medi detects damaged DNA, it halts cell division and stimu- cine have further reported that cigarette smoke causes mu- lates the activity of special enzymes to repair the damage. tations in the p53 gene. This study, published in 1995,rein- Once the DNA has been repaired, p53 allows cell division orced the strong link between smoking and cancer to continue. In cases where the DNA is irreparable, P53 described in chapter 18 then directs the cell to kill itself, activating an apoptosis NORMAL p53 ws cells with aired DNA to divide DNA repair enzyme DNA damage is caused Cell division stops, and p53 triggers iggers the destruction of cells at radiation o enzymes to repair damaged region ABNORMAL p53 Cancer Stage 1 Stage 2 Stage 3 DNA damage is caused The p53 protein fails to stop Damaged cells continue to divide by heat, radiation, or If other damage accumulates, the hemicals Cell divides without repair cell can turn cancerous damaged DNA. FIGURE 11.20 Cell division and p53 protein. Normal p53 protein monitors dNA, destroying cells with irreparable damage to their DNA. Abnormal p53 protein fails to stop cell division and repair DNA. As damaged cells proliferate, cancer develops 222 Part IV Reproduction and Heredity

Cancer and the Control of Cell Proliferation The unrestrained, uncontrolled growth of cells, called cancer, is addressed more fully in chapter 18. However, cancer certainly deserves mention in a chapter on cell di￾vision, as it is essentially a disease of cell division—a fail￾ure of cell division control. Recent work has identified one of the culprits. Working independently, cancer scientists have repeatedly identified what has proven to be the same gene! Officially dubbed p53 (researchers italicize the gene symbol to differentiate it from the protein), this gene plays a key role in the G1 checkpoint of cell division. The gene’s product, the p53 protein, monitors the integrity of DNA, checking that it is undamaged. If the p53 protein detects damaged DNA, it halts cell division and stimu￾lates the activity of special enzymes to repair the damage. Once the DNA has been repaired, p53 allows cell division to continue. In cases where the DNA is irreparable, p53 then directs the cell to kill itself, activating an apoptosis (cell suicide) program (see chapter 17 for a discussion of apoptosis). By halting division in damaged cells, p53 prevents the development of many mutated cells, and it is therefore con￾sidered a tumor-suppressor gene (even though its activities are not limited to cancer prevention). Scientists have found that p53 is entirely absent or damaged beyond use in the majority of cancerous cells they have examined! It is pre￾cisely because p53 is nonfunctional that these cancer cells are able to repeatedly undergo cell division without being halted at the G1 checkpoint (figure 11.20). To test this, sci￾entists administered healthy p53 protein to rapidly dividing cancer cells in a petri dish: the cells soon ceased dividing and died. Scientists at Johns Hopkins University School of Medi￾cine have further reported that cigarette smoke causes mu￾tations in the p53 gene. This study, published in 1995, rein￾forced the strong link between smoking and cancer described in chapter 18. 222 Part IV Reproduction and Heredity DNA damage is caused by heat, radiation, or chemicals. DNA repair enzyme p53 allows cells with repaired DNA to divide. Stage 1 DNA damage is caused by heat, radiation, or chemicals. Stage 1 The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA. Stage 2 Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous. Stage 3 Cell division stops, and p53 triggers enzymes to repair damaged region. Stage 2 p53 triggers the destruction of cells damaged beyond repair. Cancer cell ABNORMAL p53 NORMAL p53 FIGURE 11.20 Cell division and p53 protein. Normal p53 protein monitors DNA, destroying cells with irreparable damage to their DNA. Abnormal p53 protein fails to stop cell division and repair DNA. As damaged cells proliferate, cancer develops

Growth factors and cancer How do growth factors influence the cell cycle? As have seen, there are two different approaches, one pos factor and the other negative Proto-oncogenes. PDGF and many other growth fac- tors utilize the positive approach, stimulating cell divi Time(h) sion. They trigger passage through the gi checkpoint by s G2 MCG aiding the formation of cyclins and so activating genes that promote cell division. genes that normally stimulate cell division are sometimes called proto-oncogenes because FIGURE 11.21 mutations that cause them to be overexpressed or hyper The role of myc in triggering cell division. The addition of a active convert them into oncogenes(Greek onco,"can- growth factor leads to transcription of the ryc gene and rapidly ) leading to the excessive increasing levels of the myc protein. This causes Go cells to enter cell proliferation that is the S phase and begin proliferating characteristic of cancer. Even a single mutation(creating a heterozygote)can lead to cancer if the other cancer preventing genes are nonfunctional. Geneticists, using Growth Mendel's terms, call such mutations of proto-oncogenes dominant Key proteins associated Some 30 different proto-oncogenes are known. Some vith human cancers act very quickly after stimulation by growth factors More per cell in Among the most intensively studied of these are myc, fos, many breast cancers and jun, all of which cause unrestrained cell growth and eceptor division when they are overexpressed. In a normal cell, Ras Activated by mutations the myc proto-oncogene appears to be important in regu- g the gi checkpoint. Cells in which myc expression prevented will not divide, even in the presence of growth Src Activated by mutations kinase in 2-5% of all cancers factors. A critical activity of myc and other genes in this group of immediately responding proto-oncogenes Is Rb Mutated in 40% Cell cycle of all cancers stimulate a second group of"delayed response " genes, in- checkpoints cluding those that produce cyclins and Cdk proteins(fig- Mutated in 50% f all cancers ure11.21) Mammalian cell Tumor-suppressor Genes. Other growth factors utilize FIGURE 11.22 sage through the Gi checkpoint by preventing cyclins from components of the cell division-signaling pathway are responsible binding to Cdk, thus inhibiting cell division. Genes that for many cancers. Among them are proto-oncogenes encoding normally inhibit cell division are called tumor-suppressor growth factor receptors, such as ras protein, and kinase enzymes, genes. When mutated, they can also lead to unrestrained such as src, that aid ras function. Mutations that disrupt tumor cell division, but only if both copies of the gene are mutant. pressor proteins, such as rb and p53, also foster cancer Hence, these cancer-causing mutations are recessive development The most thoroughly understood of the tumor-suppressor genes is the retinoblastoma(Rb)gene. This gene was orig- ally cloned from children with a rare form of eye cancer them to act and so promoting cell division. growth fac- inherited as a recessive trait, implying that the normal tors lessen the inhibition the rb protein imposes by acti gene product was a cancer suppressor that helped keep vating kinases that phosphorylate it. Free of Rb protein ivision in check. The Rb gene encodes a protein pre- inhibition, cells begin to produce cyclins and Cdk, pass phorylation. In Go phase, the rb protein is dephosphory lated. In this state, it binds to and ties up a set of regula- The progress of mitosis is regulated by the interaction tory proteins, like myc and fos, needed for cell of two key classes of proteins, cyclin-dependent protein proliferation, blocking their action and so inhibiting cell kinases and cyclins. Some growth factors accelerate the division(see figure 11. 19). When phosphorylated, the rb cycle by protein releases its captive regulatory proteins, freeing suppress it by inhibiting their action. Chapter 11 How Cells Divide 223

Growth Factors and Cancer How do growth factors influence the cell cycle? As you have seen, there are two different approaches, one positive and the other negative. Proto-oncogenes. PDGF and many other growth fac￾tors utilize the positive approach, stimulating cell divi￾sion. They trigger passage through the G1 checkpoint by aiding the formation of cyclins and so activating genes that promote cell division. Genes that normally stimulate cell division are sometimes called proto-oncogenes because mutations that cause them to be overexpressed or hyper￾active convert them into oncogenes (Greek onco, “can￾cer”), leading to the excessive cell proliferation that is characteristic of cancer. Even a single mutation (creating a heterozygote) can lead to cancer if the other cancer￾preventing genes are nonfunctional. Geneticists, using Mendel’s terms, call such mutations of proto-oncogenes dominant. Some 30 different proto-oncogenes are known. Some act very quickly after stimulation by growth factors. Among the most intensively studied of these are myc, fos, and jun, all of which cause unrestrained cell growth and division when they are overexpressed. In a normal cell, the myc proto-oncogene appears to be important in regu￾lating the G1 checkpoint. Cells in which myc expression is prevented will not divide, even in the presence of growth factors. A critical activity of myc and other genes in this group of immediately responding proto-oncogenes is to stimulate a second group of “delayed response” genes, in￾cluding those that produce cyclins and Cdk proteins (fig￾ure 11.21). Tumor-suppressor Genes. Other growth factors utilize a negative approach to cell cycle control. They block pas￾sage through the G1 checkpoint by preventing cyclins from binding to Cdk, thus inhibiting cell division. Genes that normally inhibit cell division are called tumor-suppressor genes. When mutated, they can also lead to unrestrained cell division, but only if both copies of the gene are mutant. Hence, these cancer-causing mutations are recessive. The most thoroughly understood of the tumor-suppressor genes is the retinoblastoma (Rb) gene. This gene was orig￾inally cloned from children with a rare form of eye cancer inherited as a recessive trait, implying that the normal gene product was a cancer suppressor that helped keep cell division in check. The Rb gene encodes a protein pre￾sent in ample amounts within the nucleus. This protein interacts with many key regulatory proteins of the cell cycle, but how it does so depends upon its state of phos￾phorylation. In G0 phase, the Rb protein is dephosphory￾lated. In this state, it binds to and ties up a set of regula￾tory proteins, like myc and fos, needed for cell proliferation, blocking their action and so inhibiting cell division (see figure 11.19). When phosphorylated, the Rb protein releases its captive regulatory proteins, freeing them to act and so promoting cell division. Growth fac￾tors lessen the inhibition the Rb protein imposes by acti￾vating kinases that phosphorylate it. Free of Rb protein inhibition, cells begin to produce cyclins and Cdk, pass the G1 checkpoint, and proceed through the cell cycle. Figure 11.22 summarizes the types of genes that can cause cancer when mutated. The progress of mitosis is regulated by the interaction of two key classes of proteins, cyclin-dependent protein kinases and cyclins. Some growth factors accelerate the cell cycle by promoting cyclins and Cdks, others suppress it by inhibiting their action. Chapter 11 How Cells Divide 223 Time (h) 0 8 16 24 G0 S M G2 C G1 Growth factor Levels of myc protein FIGURE 11.21 The role of myc in triggering cell division. The addition of a growth factor leads to transcription of the myc gene and rapidly increasing levels of the myc protein. This causes G0 cells to enter the S phase and begin proliferating. Growth factor receptor More per cell in many breast cancers Ras protein Activated by mutations of ras in 20–30% of all cancers Src kinase Activated by mutations in 2–5% of all cancers Rb protein Mutated in 40% of all cancers p53 protein Mutated in 50% of all cancers Key proteins associated with human cancers Growth factor receptor Ras protein Src kinase p53 protein Rb protein Cell cycle checkpoints Mammalian cell Cytoplasm Nucleus FIGURE 11.22 Mutations cause cancer. Mutations in genes encoding key components of the cell division-signaling pathway are responsible for many cancers. Among them are proto-oncogenes encoding growth factor receptors, such as ras protein, and kinase enzymes, such as src, that aid ras function. Mutations that disrupt tumor￾suppressor proteins, such as Rb and p53, also foster cancer development

Chapter 1I http://www.mhhe.com/raven6ehttp://www.biocourse.com Questions Media resource 11.1 Bacteria divide far more simply than do eukaryotes Cell division Bacterial cells divide by simple binary fission 1. How is the genome The two replicated circular DNa molecules attach to replicated prior to binary fission the plasma membrane at different points, and fission in a bacterial cell? is initiated between those points karyote Scientists on sci 11.2 Chromosomes are highly ordered structures. Eukaryotic DNA forms a complex with histones and 2. What are nucleosomes · Chromosomes other proteins and is packaged into chromosomes. In eukaryotic cells, DNA replication is completed articipate in the coiling of during the S phase of the cell cycle, and during the Ga phase the cell makes its final preparation for 3. What are the differences Mitosis. Along with G, these two phases constitute the 4. What is a karyotype? How portion of the cell cycle called interphase, which are chromosomes alternates with mitosis and cytokinesis from one another in a karyotype? 11.3 Mitosis is a key phase of the cell cycle The first stage of mitosis is prophase, during whic 5. Which the · Art Activity: Mitosis the mitotic spindle apparatus forms cycle is generally the longest in Art Activity: Plant In the second stage of mitosis, metaphase, the the cells of a mature eukaryote? Cell mitosis hromosomes are arranged in a circle around the 6. What happens to the periphery of th At the beginning of the third stage of mitosis, 7. What changes with respect anaphase, the centromeres joining each pair of sister to ribosomal rNa occur during chromatids separate, freeing the sister chromat prophase? from each other 8. What event signals the nitiation of metaphase? After the chromatids physically separate, they are 9. What molecular mechanism pulled to opposite poles of the cell by the seems to be responsible for the microtubules attached to their centromeres movement of the poles during Student research: In the fourth and final stage of mitosis, telophase, the anaphase Nuclear Division in mitotic apparatus is disassembled, the nuclear 10. Describe three events that envelope re-forms, and the chromosomes uncoil occur during telophase. When mitosis is complete, the cell divides in two, so 11. How is cytokinesis in animal that the two sets of chromosomes separated by cells different from that in plant mitosis end up in different daughter cells 11.4 The cell cycle is carefully controlled. The cell cycle is regulated by two types of proteins, 12. What aspects of the cell Exploration: cyclins and cyclin-dependent protein kinases, which cycle are controlled by the Gl, Regulating the cell permit progress past key"checkpoints"in the cell Gz, and M checkpoints? How cycle only if the cell is ready to proceed further are cyclins and cyclin-depe ndent Failures of cell cycle regulation can lead to cycle regulation at checkpoints? uncontrolled cell growth and lie at the root of cancer 224 Part IV Reproduction and Heredity

224 Part IV Reproduction and Heredity Chapter 11 Summary Questions Media Resources 11.1 Bacteria divide far more simply than do eukaryotes. • Bacterial cells divide by simple binary fission. • The two replicated circular DNA molecules attach to the plasma membrane at different points, and fission is initiated between those points. 1. How is the genome replicated prior to binary fission in a bacterial cell? • Eukaryotic DNA forms a complex with histones and other proteins and is packaged into chromosomes. • In eukaryotic cells, DNA replication is completed during the S phase of the cell cycle, and during the G2 phase the cell makes its final preparation for mitosis. • Along with G1, these two phases constitute the portion of the cell cycle called interphase, which alternates with mitosis and cytokinesis. 2. What are nucleosomes composed of, and how do they participate in the coiling of DNA? 3. What are the differences between heterochromatin and euchromatin? 4. What is a karyotype? How are chromosomes distinguished from one another in a karyotype? 11.2 Chromosomes are highly ordered structures. • The first stage of mitosis is prophase, during which the mitotic spindle apparatus forms. • In the second stage of mitosis, metaphase, the chromosomes are arranged in a circle around the periphery of the cell. • At the beginning of the third stage of mitosis, anaphase, the centromeres joining each pair of sister chromatids separate, freeing the sister chromatids from each other. • After the chromatids physically separate, they are pulled to opposite poles of the cell by the microtubules attached to their centromeres. • In the fourth and final stage of mitosis, telophase, the mitotic apparatus is disassembled, the nuclear envelope re-forms, and the chromosomes uncoil. • When mitosis is complete, the cell divides in two, so that the two sets of chromosomes separated by mitosis end up in different daughter cells. 5. Which phases of the cell cycle is generally the longest in the cells of a mature eukaryote? 6. What happens to the chromosomes during S phase? 7. What changes with respect to ribosomal RNA occur during prophase? 8. What event signals the initiation of metaphase? 9. What molecular mechanism seems to be responsible for the movement of the poles during anaphase? 10. Describe three events that occur during telophase. 11. How is cytokinesis in animal cells different from that in plant cells? 11.3 Mitosis is a key phase of the cell cycle. • The cell cycle is regulated by two types of proteins, cyclins and cyclin-dependent protein kinases, which permit progress past key “checkpoints” in the cell cycle only if the cell is ready to proceed further. • Failures of cell cycle regulation can lead to uncontrolled cell growth and lie at the root of cancer. 12. What aspects of the cell cycle are controlled by the G1, G2, and M checkpoints? How are cyclins and cyclin-dependent protein kinases involved in cell cycle regulation at checkpoints? 11.4 The cell cycle is carefully controlled. http://www.mhhe.com/raven6e http://www.biocourse.com • Cell Division Introduction • Prokaryotes • Scientists on Science: Ribozymes • Art Activity: Mitosis Overview • Art Activity: Plant Cell Mitosis • Mitosis • Mitosis • Student Research: Nuclear Division in Drosophila • Chromosomes • Exploration: Regulating the cell cycle