The Cell Cycle and Cell Division 7

Chapter 7 The Cell Cycle and Cell Division Key Concepts 7.1 Different Life Cycles Use Different Modes of Cell Reproduction 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells 7.3 Cell Reproduction Is Under Precise Control

Chapter 7 The Cell Cycle and Cell Division Key Concepts 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity 7.5 Programmed Cell Death Is a Necessary Process in Living Organisms

Chapter 7 Opening Question How does infection with HPV result in uncontrolled cell reproduction?

Concept 7.1 Different Life Cycles Use Different Modes of Cell Reproduction The lifespan of an organism is linked to cell reproduction—usually called cell division. Organisms have two basic strategies for reproducing themselves: Asexual reproduction Sexual reproduction Cell division is also important in growth and repair of tissues.

Figure 7.1 The Importance of Cell Division (Part 1)

Figure 7.1 The Importance of Cell Division (Part 2)

Figure 7.1 The Importance of Cell Division (Part 3)

Concept 7.1 Different Life Cycles Use Different Modes of Cell Reproduction In asexual reproduction the offspring are clones—genetically identical to the parent. Any genetic variations are due to mutations. A unicellular prokaryote may reproduce itself by binary fission. Single-cell eukaryotes can reproduce by mitosis. Other eukaryotes are also able to reproduce through asexual or sexual means.

Figure 7.2 Asexual Reproduction on a Large Scale

Concept 7.1 Different Life Cycles Use Different Modes of Cell Reproduction Sexual reproduction requires gametes—two parents each contribute one gamete to an offspring. Gametes form by meiosis—a process of cell division. Gametes—and offspring—differ genetically from each other and from the parents.

Concept 7.1 Different Life Cycles Use Different Modes of Cell Reproduction DNA in eukaryotic cells is organized into chromosomes. A chromosome consists of a single molecule of DNA and proteins. Somatic cells—body cells not specialized for reproduction Each somatic cell contains two sets of chromosomes (homologs) that occur in homologous pairs.

Concept 7.1 Different Life Cycles Use Different Modes of Cell Reproduction Gametes contain only one set of chromosomes—one homolog from each pair. Haploid cell—Number of chromosomes = n Fertilization—Two haploid gametes (female egg and male sperm) fuse to form a zygote. Chromosome number in zygote = 2n and cells are diploid.

Concept 7.1 Different Life Cycles Use Different Modes of Cell Reproduction All kinds of sexual life cycles involve meiosis: Haplontic life cycle—in protists, fungi, and some algae—zygote is only diploid stage After zygote forms it undergoes meiosis to form haploid spores, which germinate to form a new organism. Organism is haploid, and produces gametes by mitosis—cells fuse to form diploid zygote.

Figure 7.3 All Sexual Life Cycles Involve Fertilization and Meiosis (Part 1)

Concept 7.1 Different Life Cycles Use Different Modes of Cell Reproduction Alternation of generations—most plants, some protists; meiosis gives rise to haploid spores Spores divide by mitosis to form the haploid generation (gametophyte). Gametophyte forms gametes by mitosis. Gametes then fuse to form diploid zygote (sporophyte), which in turn produces haploid spores by meiosis.

Figure 7.3 All Sexual Life Cycles Involve Fertilization and Meiosis (Part 2)

Concept 7.1 Different Life Cycles Use Different Modes of Cell Reproduction Diplontic life cycle—animals and some plants; gametes are the only haploid stage A mature organism is diploid and produces gametes by meiosis. Gametes fuse to form diploid zygote; zygote divides by mitosis to form mature organism.

Figure 7.3 All Sexual Life Cycles Involve Fertilization and Meiosis (Part 3)

Concept 7.1 Different Life Cycles Use Different Modes of Cell Reproduction The essence of sexual reproduction is that it allows the random selection of half the diploid chromosome set. This forms a haploid gamete that fuses with another to make a diploid cell. Thus, no two individuals have exactly the same genetic makeup.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Four events must occur for cell division: Reproductive signal—to initiate cell division Replication of DNA Segregation—distribution of the DNA into the two new cells Cytokinesis—division of the cytoplasm and separation of the two new cells

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells In prokaryotes, cell division results in reproduction of the entire organism. The cell: Grows in size Replicates its DNA Separates the DNA and cytoplasm into two cells through binary fission

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Most prokaryotes have one chromosome, a single molecule of DNA—usually circular. Two important regions in reproduction: ori - where replication starts ter - where replication ends

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Replication occurs as the DNA is threaded through a “replication complex” of proteins in the center of the cell. Replication begins at the ori site and moves towards the ter site.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells As replication proceeds, the ori complexes move to opposite ends of the cell. DNA sequences adjacent to the ori region actively bind proteins for the segregation, hydrolyzing ATP for energy. An actin-like protein provides a filament along which ori and other proteins move.

Figure 7.4 Prokaryotic Cell Division

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Cytokinesis begins after chromosome segregation by a pinching in of the plasma membrane—protein fibers form a ring. As the membrane pinches in, new cell wall materials are synthesized resulting in separation of the two cells.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Eukaryotic cells divide by mitosis followed by cytokinesis. Replication of DNA occurs as long strands are threaded through replication complexes. DNA replication only occurs during a specific stage of the cell cycle.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells In segregation of DNA after cell division, one copy of each chromosome ends up in each of the two new cells. In eukaryotes, the chromosomes become highly condensed. Mitosis segregates them into two new nuclei— the cytoskeleton is involved in the process.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Cytokinesis follows mitosis. The process in plant cells (which have cell walls) is different than in animal cells (which do not have cell walls).

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells The cell cycle—the period between cell divisions In eukaryotes it is divided into mitosis and cytokinesis—called the M phase—and a long interphase. During interphase, the cell nucleus is visible and cell functions including replication occur Interphase begins after cytokinesis and ends when mitosis starts.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Interphase has three subphases: G1, S, and G2. G1 (Gap 1)—variable, a cell may spend a long time in this phase carrying out its functions S phase (Synthesis)—DNA is replicated G2 (Gap 2)—the cell prepares for mitosis, synthesizes microtubules for segregating chromosomes

Figure 7.5 The Phases of the Eukaryotic Cell Cycle (Part 1)

Figure 7.5 The Phases of the Eukaryotic Cell Cycle (Part 2)

Figure 7.5 The Phases of the Eukaryotic Cell Cycle (Part 3)

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells In mitosis, one nucleus produces two daughter nuclei each containing the same number of chromosomes as the parent nucleus. Mitosis is continuous, but can be can be divided into phases—prophase, prometaphase, metaphase, anaphase, and telophase.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells During interphase, only the nuclear envelope and and the nucleolus are visible. The chromatin (DNA) is not yet condensed. Three structures appear in prophase: The condensed chromosomes Centrosome Spindle

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Condensed chromosomes appear during prophase. Sister chromatids—two DNA molecules on each chromosome after replication Centromere—region where chromatids are joined Kinetochores are protein structures on the centromeres, and are important for chromosome movement.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells The karyotype of an organism reflects the number and sizes of its condensed chromosomes. Karyotype analysis can be used to identify organisms, but DNA sequence is more commonly used.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Segregation is aided by other structures: The centrosome determines the orientation of the spindle apparatus. Each centrosome can consist of two centrioles—hollow tubes formed by microtubules. Centrosome is duplicated during S phase and each moves towards opposite sides of the nucleus.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Centrosomes serve as mitotic centers or poles; the spindle forms between the poles from two types of microtubules: Polar microtubules form a spindle and overlap in the center. Kinetochore microtubules—attach to kinetochores on the chromatids. Sister chromatids attach to opposite halves of the spindle.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Chromosome separation and movement is highly organized. During prometaphase, the nuclear envelope breaks down. Chromosomes consisting of two chromatids attach to the kinetochore mictotubules.

Figure 7.6 The Phases of Mitosis (1)

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Durin metaphase, chromosomes line up at the midline of the cell. During anaphase, the separation of sister chromatids is controlled by M phase cyclin- Cdk; cohesin is hydrolyzed by separase. After separation, they move to opposite ends of the spindle and are referred to as daughter chromosomes.

Figure 7.6 The Phases of Mitosis (2)

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells A protein at the kinetochores—cytoplasmic dynein—hydrolyzes ATP for energy to move chromosomes along the microtubules towards the poles. Microtubules also shorten, drawing chromosomes toward poles.

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Telophase occurs after chromosomes have separated: Spindle breaks down Chromosomes uncoil Nuclear envelope and nucleoli appear Two daughter nuclei are formed with identical genetic information

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Cytokinesis: Division of the cytoplasm differs in plant and animals In animal cells, plasma membrane pinches between the nuclei because of a contractile ring of microfilaments of actin and myosin.

Figure 7.7 Cytokinesis Differs in Animal and Plant Cells (Part 1)

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells Plant cells: Vesicles from the Golgi apparatus appear along the plane of cell division These fuse to form a new plasma membrane. Contents of vesicles form the cell plate—the beginning of the new cell wall.

Figure 7.7 Cytokinesis Differs in Animal and Plant Cells (Part 2)

Concept 7.2 Both Binary Fission and Mitosis Produce Genetically Identical Cells After cytokinesis: Each daughter cell contains all of the components of a complete cell. Chromosomes are precisely distributed. The orientation of cell division is important to development, but organelles are not always evenly distributed.

Concept 7.3 Cell Reproduction Is Under Precise Control The reproductive rates of most prokaryotes respond to environmental conditions. In eukaryotes, cell division is related to the needs of the entire organism. Cells divide in response to extracellular signals, like growth factors.

Concept 7.3 Cell Reproduction Is Under Precise Control The eukaryotic cell cycle has four stages: G1, S, G2, and M. Progression is tightly regulated—the G1-S transition is called R, the restriction point. Passing this point usually means the cell will proceed with the cell cycle and divide.

Figure 7.8 The Eukaryotic Cell Cycle

Concept 7.3 Cell Reproduction Is Under Precise Control Specific signals trigger the transition from one phase to another. Evidence for substances as triggers came from cell fusion experiments. Nuclei in cells at different stages, fused by polyethylene glycol, both entered the phase of DNA replication (S).

Figure 7.9 Regulation of the Cell Cycle (Part 1)

Concept 7.3 Cell Reproduction Is Under Precise Control Transitions also depend on activation of cyclin- dependent kinases (Cdk’s). A protein kinase is an enzyme that catalyzes phosphorylation from ATP to a protein. Phosphorylation changes the shape and function of a protein by changing its charges.

Concept 7.3 Cell Reproduction Is Under Precise Control Cdk is activated by binding to cyclin (by allosteric regulation); this alters its shape and exposes its active site. The G1-S cyclin-Cdk complex acts as a protein kinase and triggers transition from G1 to S. Other cyclin-Cdk’s act at different stages of the cell cycle, called cell cycle checkpoints.

Figure 7.10 Cyclins Are Transient in the Cell Cycle

Concept 7.3 Cell Reproduction Is Under Precise Control Example of G1-S cyclin-Cdk regulation: Progress past the restriction point in G1 depends on retinoblastoma protein (RB). RB normally inhibits the cell cycle, but when phosphorylated by G1-S cyclin-Cdk, RB becomes inactive and no longer blocks the cell cycle.

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity Meiosis consists of two nuclear divisions but DNA is replicated only once. The function of meiosis is to: Reduce the chromosome number from diploid to haploid Ensure that each haploid has a complete set of chromosomes Generate diversity among the products

Figure 7.11 Mitosis and Meiosis: A Comparison

Figure 7.12 Meiosis: Generating Haploid Cells (Part 1)

Figure 7.12 Meiosis: Generating Haploid Cells (Part 2)

Figure 7.12 Meiosis: Generating Haploid Cells (Part 3)

Figure 7.12 Meiosis: Generating Haploid Cells (Part 4)

Figure 7.12 Meiosis: Generating Haploid Cells (Part 5)

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity Meiotic division reduces the chromosome number. Two unique features: In meiosis I, homologous pairs of chromosomes come together and line up along their entire lengths. After metaphase I, the homologous chromosome pairs separate, but individual chromosomes made up of two sister chromatids remain together.

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity Meiosis I is preceded by an S phase during which DNA is replicated. Each chromosome then consists of two sister chromatids, held together by cohesin proteins. At the end of meiosis I, two nuclei form, each with half the original chromosomes—still composed of sister chromatids.

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity Sister chromatids separate during meiosis II, which is not proceeded by DNA replication. The products of meiosis I and II are four cells with a haploid number of chromosomes. These four cells are not genetically identical. Two processes may occur: Crossing over and independent assortment

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity In prophase of meiosis I homologous chromosomes pair by synapsis. The four chromatids of each pair of chromosomes form a tetrad,or bivalent. The homologs seem to repel each other but are held together at chiasmata.

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity Crossing over is an exchange of genetic material that occurs at the chiasma. Crossing over results in recombinant chromatids and increases genetic variability of the products.

In-Text Art, Ch. 7, p. 138

Figure 7.13 Crossing Over Forms Genetically Diverse Chromosomes

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity Prophase I may last a long time. Human males: Prophase I lasts about 1 week, and 1 month for entire meiotic cycle Human females: Prophase I begins before birth, and ends up to decades later during the monthly ovarian cycle

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity Independent assortment during anaphase I also allows for chance combinations and genetic diversity. After homologous pairs of chromosomes line up at metaphase I, it is a matter of chance which member of a pair goes to which daughter cell. The more chromosomes involved, the more combinations possible.

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity Meiotic errors: Nondisjunction—homologous pairs fail to separate at anaphase I—sister chromatids fail to separate, or homologous chromosomes may not remain together Either results in aneuploidy—chromosomes lacking or present in excess

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity Organisms with triploid (3n), tetraploid (4n), and even higher levels are called polyploid. This can occur through an extra round of DNA duplication before meiosis, or the lack of spindle formation in meiosis II. Polyploidy occurs naturally in some species, and can be desirable in plants.

Concept 7.4 Meiosis Halves the Nuclear Chromosome Content and Generates Diversity If crossing over happens between non- homologous chromosomes, the result is a translocation. A piece of chromosome may rejoin another chromosome, and its location can have profound effects on the expression of other genes. Example: Leukemia

In-Text Art, Ch. 7, p. 140

Concept 7.5 Programmed Cell Death Is a Necessary Process in Living Organisms Cell death occurs in two ways: In necrosis, the cell is damaged or starved for oxygen or nutrients. The cell swells and bursts. Cell contents are released to the extracellular environment and can cause inflammation.

7.5 ProConcept 7.ammed Cell Death Is a Necessary Process in Living Organisms Apoptosis is genetically programmed cell death. Two possible reasons: The cell is no longer needed, e.g., the connective tissue between the fingers of a fetus. Old cells may be prone to genetic damage that can lead to cancer—blood cells and epithelial cells die after days or weeks.

Concept 7.5 Programmed Cell Death Is a Necessary Process in Living Organisms Events of apoptosis: Cell detaches from its neighbors Cuts up its chromatin into nucleosome-sized pieces Forms membranous lobes called “blebs” that break into fragments Surrounding living cells ingest the remains of the dead cell

Figure 7.14 Apoptosis: Programmed Cell Death (Part 1)

Concept 7.5 Programmed Cell Death Is a Necessary Process in Living Organisms Cell death cycle is controlled by signals: Lack of a mitotic signal (growth factor) Recognition of damaged DNA External signals cause membrane proteins to change shape and activate enzymes called caspases—hydrolyze proteins of membranes.

Figure 7.14 Apoptosis: Programmed Cell Death (Part 2)

Answer to Opening Question Human papilloma virus (HPV) stimulates the cell cycle when it infects the cervix. Two proteins regulate the cell cycle: Oncogene proteins are positive regulators of the cell cycle—in cancer cells they are overactive or present in excess Tumor suppressors are negative regulators of the cell cycle, but in cancer cells they are inactive—can be blocked by a virus such as HPV

Figure 7.15 Molecular Changes Regulate the Cell Cycle in Cancer Cells