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Lecture 11 students - Lecture 11 How Do Prokaryo1c...

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Unformatted text preview: Lecture 11 How Do Prokaryo1c and Eukaryo1c Cells Divide? The life cycle of an organism is linked to cell division. Unicellular organisms use cell division primarily for reproduc1on. In mul1cellular organisms, cell division is also important in growth and repair of 1ssues. Figure 11.1 Important Consequences of Cell Division How Do Prokaryo1c and Eukaryo1c Cells Divide? Four events must occur for cell division: •  Reproduc)ve signal: To ini1ate cell division •  Replica)on: Of DNA •  Segrega)on: Distribu1on of the DNA into the two new cells •  Cytokinesis: Separa1on of the two new cells How Do Prokaryo1c and Eukaryo1c Cells Divide? In prokaryotes, binary fission results in two new cells. For many bacteria, abundant food supplies speed up the division cycle. How Do Prokaryo1c and Eukaryo1c Cells Divide? Most prokaryotes have one chromosome, a single molecule of DNA—usually circular. Two important regions in reproduc1on: •  ori—where replica1on starts •  ter—where replica1on ends How Do Prokaryo1c and Eukaryo1c Cells Divide? Replica1on occurs as the DNA is threaded through a “replica1on complex” of proteins in the center of the cell. Replica1on begins at the ori site and moves towards the ter site. Figure 11.2 Prokaryo1c Cell Division (Part 1) Figure 11.2 Prokaryo1c Cell Division (Part 2) How Do Prokaryo1c and Eukaryo1c Cells Divide? In eukaryotes, signals for cell division are related to the needs of the en1re organism. Eukaryotes usually have many chromosomes; the processes of replica.on and segrega.on are more intricate. How Do Prokaryo1c and Eukaryo1c Cells Divide? DNA replica1on usually occurs between cell divisions. Sister chroma)ds—newly replicated chromosomes are closely associated. Mitosis separates them into two new nuclei, iden1cal to the parent cell. How Is Eukaryo1c Cell Division Controlled? Meiosis is nuclear division in cells involved in sexual reproduc1on. The cells resul1ng from meiosis are not iden1cal to the parent cells. How Is Eukaryo1c Cell Division Controlled? The cell cycle: The period between cell divisions, divided into mitosis/cytokinesis and interphase. Interphase: The cell nucleus is visible and cell func1ons including replica1on occur. Interphase begins aXer cytokinesis and ends when mitosis starts. Figure 11.3 The Eukaryo1c Cell Cycle How Is Eukaryo1c Cell Division Controlled? Interphase has three subphases: G1, S, and G2 •  G1: Gap 1—between end of cytokinesis and onset of S phase; chromosomes are single, unreplicated structures How Is Eukaryo1c Cell Division Controlled? •  Restric)on point—at the G1 ­to ­S transi1on a commitment is made to DNA replica1on and cell division •  S phase: DNA replicates; one chromosome becomes two sister chroma1ds •  G2: Gap 2—end of S phase, cell prepares for mitosis •  M phase: Mitosis and cytokinesis occur during this phase Figure 11.4 Regula1on of the Cell Cycle How Is Eukaryo1c Cell Division Controlled? Transi1ons also depend on ac1va1on of cyclin ­dependent kinases (Cdk’s). A protein kinase is an enzyme that catalyzes phosphoryla1on from ATP to a protein. Phosphoryla1on changes the shape and func1on of a protein by changing its charges. How Is Eukaryo1c Cell Division Controlled? Cdk is ac1vated by binding to cyclin (by allosteric regula.on); this alters its shape and exposes its ac1ve site. The G1 ­S cyclin ­Cdk complex acts as a protein kinase and triggers transi1on from G1 to S. Other cyclin ­Cdk’s act at different stages of the cell cycle. Figure 11.5 Cyclin Binding Ac1vates Cdk How Is Eukaryo1c Cell Division Controlled? Example of G1 ­S cyclin ­Cdk regula1on: Progress past the restric1on point in G1 depends on re.noblastoma protein (RB). RB normally inhibits the cell cycle, but when phosphorylated by G1 ­S cyclin ­Cdk, RB becomes inac1ve and no longer blocks the cell cycle. Figure 11.6 Cyclin ­Dependent Kinases Regulate Progress Through the Cell Cycle How Is Eukaryo1c Cell Division Controlled? Because different cyclin ­Cdk complexes regulate stages of the cell cycle, regula1ng Cdk’s is key to regula1ng cell division. Cdk’s can be regulated by the presence or absence of cyclins. Figure 11.7 Cyclins Are Transient in the Cell Cycle How Is Eukaryo1c Cell Division Controlled? Cyclin ­Cdk’s act at cell cycle checkpoints to regulate progress. Example: If DNA is damaged during G1, p21 protein is made. p21 binds to G1 Cdk’s, preven1ng their ac1va1on. The cell cycle stops while DNA is repaired. How Is Eukaryo1c Cell Division Controlled? Some cells no longer divide, or divide infrequently and need signals. •  Growth factors: External chemical signals that s1mulate these cells to divide •  Platelet ­derived growth factor: From platelets that ini1ate blood cloeng, s1mulates skin cells to divide and heal wounds What Happens during Mitosis? AXer DNA replicates, its segrega1on occurs during mitosis. The DNA molecule is complexed with proteins to form dense chroma)n. Condensins coat DNA—make it compact. The sister chroma1ds are held together by cohesin, which is removed during mitosis except at the centromere. Figure 11.8 Chromosomes, Chroma1ds, and Chroma1n What Happens during Mitosis? DNA molecules are extensively “packed” even during interphase. Packing is achieved by histones—proteins with posi1ve charges that ahract nega1ve phosphate groups of DNA. Interac1ons result in the forma1on of beadlike units, or nucleosomes. Figure 11.9 DNA is Packed into a Mito1c Chromosome (Part 1) Figure 11.9 DNA is Packed into a Mito1c Chromosome (Part 2) What Happens during Mitosis? Segrega1on is aided by other structures: •  The centrosome determines the plane of cell division •  It doubles during S phase and will determine the spindle orienta1on •  Each centrosome can consist of two centrioles—hollow tubes formed by microtubules—at right angles What Happens during Mitosis? The centrosomes move to opposite ends of the nuclear envelope during G2 ­to ­M transi1on. Orienta1on determines the plane at which the cell will divide and the spa1al rela1onship of the two new cells. What Happens during Mitosis? Mitosis can be divided into phases: •  Prophase •  Prometaphase •  Metaphase •  Anaphase •  Telophase What Happens during Mitosis? During prophase, cohesin disappears except at the centromere; chroma1ds become visible. Kinetochores, for movement, develop in the centromere regions. Centrosomes serve as mito.c centers or poles; microtubules form between the poles to make the spindle. What Happens during Mitosis? Spindle has two types of microtubules: •  Polar microtubules—form spindle; overlap in center •  Kinetochore microtubules—ahach to kinetochores on the chroma1ds. Sister chroma1ds ahach to opposite halves of the spindle The Mitotic Spindle Consists of Microtubules What Happens during Mitosis? During prometaphase, the nuclear envelope breaks down. Chromosomes consis1ng of two chroma1ds ahach to the kinetochore mictotubules. Figure 11.11 (1) The Phases of Mitosis What Happens During Mitosis? Metaphase: Chromosomes line up at the midline of the cell. Anaphase: The separa1on of sister chroma1ds is controlled by M phase cyclin ­Cdk; cohesin is hydrolyzed by separase. AXer separa1on they move to opposite ends of the spindle and are referred to as daughter chromosomes. Figure 11.11 (2) The Phases of Mitosis Figure 11.12 Chroma1d Ahachment and Separa1on What Happens During Mitosis? 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. What Happens During Mitosis? Telophase occurs aXer chromosomes have separated: •  Spindle breaks down •  Chromosomes uncoil •  Nuclear envelope and nucleoli appear •  Two daughter nuclei are formed with iden1cal gene1c informa1on What Happens During Mitosis? Cytokinesis: Division of the cytoplasm differs in plant and animals. •  Animal cells: Plasma membrane pinches between the nuclei because of a contrac.le ring of microfilaments of ac1n and myosin Figure 11.13 Cytokinesis Differs in Animal and Plant Cells (A) What Happens During Mitosis? •  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 11.13 Cytokinesis Differs in Animal and Plant Cells (B) What Role Does Cell Division Play in a Sexual Life Cycle? Asexual reproduc)on is based on mito1c division of the nucleus. •  A unicellular organism may reproduce itself •  Cells of mul1cellular organisms break off to form a new individual The offspring are clones—gene.cally iden.cal to the parent. Figure 11.14 Asexual Reproduc1on in the Large and the Small What Role Does Cell Division Play in a Sexual Life Cycle? Sexual reproduc)on: The offspring are not iden1cal to the parents. It requires gametes created by meiosis; two parents each contribute one gamete to an offspring. Gametes—and offspring—differ gene1cally from each other and from the parents. What Role Does Cell Division Play in a Sexual Life Cycle? Soma)c cells—body cells not specialized for reproduc1on. Each soma1c cell contains homologous pairs of chromosomes with corresponding genes. Each parent contributes one homolog. What Role Does Cell Division Play in a Sexual Life Cycle? Gametes contain only one set of chromosomes. •  Haploid: Number of chromosomes = n •  Fer)liza)on: Two haploid gametes (female egg and male sperm) fuse to form a diploid zygote; chromosome number = 2n What Role Does Cell Division Play in a Sexual Life Cycle? •  Several kinds of sexual life cycles •  Haplon.c life cycle: In pro1sts, fungi, and some algae—zygote is only diploid stage •  AXer zygote forms it undergoes meiosis to form haploid spores, which germinate to form a new organism •  Organism is haploid, produces gametes by mitosis—cells fuse to form zygote Figure 11.15 Fer1liza1on and Meiosis Alternate in Sexual Reproduc1on (Part 1) What Role Does Cell Division Play in a Sexual Life Cycle? Alterna)on of genera)ons: Most plants, some pro1sts—meiosis gives rise to haploid spores. Spores divide by mitosis to form the haploid genera1on (gametophyte). Gametophyte forms gametes by mitosis. Gametes fuse to form diploid zygote (sporophyte), which in turn produces gametes by meiosis. Figure 11.15 Fer1liza1on and Meiosis Alternate in Sexual Reproduc1on (Part 2) What Role Does Cell Division Play in a Sexual Life Cycle? Diplon.c life cycle: Animals and some plants; gametes are the only haploid stage. Mature organism is diploid and produces gametes by meiosis. Gametes fuse to form diploid zygote; zygote divides by mitosis to form mature organism. Figure 11.15 Fer1liza1on and Meiosis Alternate in Sexual Reproduc1on (Part 3) What Role Does Cell Division Play in a Sexual Life Cycle? Sexual reproduc1on generates diversity among individual organisms. It allows the random selec.on 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 gene1c makeup. What Role Does Cell Division Play in a Sexual Life Cycle? Karyotype: The number, shapes, and sizes of the metaphase chromosomes in a cell. Individual chromosomes can be recognized by length, posi1on of centromere, and banding paherns. Cytogene.cs uses karyotypes to aid in the diagnosis of certain diseases. Figure 11.16 The Human Karyotype What Happens during Meiosis? Meiosis consists of two nuclear divisions but DNA is replicated only once. The func1on 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 11.17 Meiosis: Genera1ng Haploid Cells (Part 1) Figure 11.17 Meiosis: Genera1ng Haploid Cells (Part 2) Figure 11.17 Meiosis: Genera1ng Haploid Cells (Part 3) Figure 11.17 Meiosis: Genera1ng Haploid Cells (Part 4) What Happens during Meiosis? Meio1c division reduces the chromosome number. Two unique features: •  In meiosis I, homologous pairs of chromosomes come together and pair along their en1re lengths •  AXer metaphase I, the homologous pairs separate, but individual chromosomes made up of sister chroma1ds remain together What Happens during Meiosis? Meiosis I is preceded by an S phase during which DNA is replicated. Each chromosome then consists of two sister chroma1ds, held together by cohesin proteins. At the end of meiosis I, two nuclei form, each with half the original chromosomes —s1ll composed of sister chroma1ds. What Happens during Meiosis? During prophase I, the homologous chromosomes pair: synapsis. The four chroma1ds of each homologous pair form a tetrad, or bivalent. What Happens during Meiosis? Prophase I and metaphase I: The chroma1n con1nues to coil and compact. The homologs seem to repel each other but are held together at chiasmata that form between non ­sister chroma1ds. What Happens during Meiosis? Exchange of gene.c material occurs at the chiasmata—called crossing over. Crossing over results in recombinant chroma1ds and increases gene1c variability of the products. Figure 11.19 Crossing Over Forms Gene1cally Diverse Chromosomes What Happens during Meiosis? Prophase I may last a long 1me. •  Human males: Prophase I lasts about 1 week, and 1 month for en1re meio1c cycle •  Human females: Prophase I begins before birth, and ends up to decades later during the monthly ovarian cycle What Happens during Meiosis? In meiosis I maternal chromosomes pair with paternal homologs during synapsis. This does not occur during mitosis. Crossing over is one reason for gene1c diversity—independent assortment during anaphase I also allows for chance combina1ons. What Happens during Meiosis Differences between meiosis II and mitosis: •  DNA does not replicate before meiosis II •  In meiosis II the sister chroma1ds may not be iden1cal because of crossing over •  The number of chromosomes at the equatorial plate in meiosis II is half the number of those in mitosis Figure 11.20 Mitosis and Meiosis: A Comparison (Part 1) Figure 11.20 Mitosis and Meiosis: A Comparison (Part 2) What Happens during Meiosis Meio1c errors: •  Nondisjunc)on: Homologous pairs fail to separate at anaphase I; sister chroma1ds fail to separate, or homologous chromosomes may not remain together •  Either results in aneuploidy—chromosomes lacking or present in excess Figure 11.21 Nondisjunc1on Leads to Aneuploidy What Happens during Meiosis Aneuploidy may be caused by lack of cohesins that hold the homologous pairs together. Without cohesins both homologs may go to the same pole. The resul1ng gamete will have two of the same chromosome, or none. What Happens during Meiosis In humans, if both chromosome 21 homologs go to the same pole and the resul1ng egg is fer1lized, it will be trisomic for chromosome 21. This results in the condi1on known as Down syndrome. A fer1lized egg that did not receive a copy of chromosome 21 will be monosomic, which is lethal. What Happens during Meiosis Transloca)on: A piece of chromosome may break away and ahach to another chromosome. An individual with a translocated piece of chromosome 21 plus two normal copies will have Down syndrome. What Happens during Meiosis Trisomies and monosomies are common in human zygotes. Most embryos from these zygotes do not survive. Trisomies and monosomies for chromosomes other than 21 are lethal—many miscarriages are due to this. What Happens during Meiosis Organisms with complete extra sets of chromosomes are called polyploid. Triploid (3n), tetraploid (4n), and even higher ploidy levels Mitosis can occur because each chromosome behaves independently. What Happens during Meiosis Polyploidy (e.g., 3n) can prevent meiosis because not all chromosomes will have a homolog, and anaphase I will not take place. Polypolidy can enhance crop plants and triploidy produces sterile trout to stock rivers. In a Living Organism, How Do Cells Die? Cell death occurs in two ways: •  Necrosis—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 inflamma1on In a Living Organism, How Do Cells Die? •  Apoptosis is gene1cally programmed cell death. Two possible reasons: Cell is no longer needed, e.g., the connec1ve 1ssue between the fingers of a fetus Old cells may be prone to gene.c damage that can lead to cancer; blood cells and epithelial cells die aXer days or weeks In a Living Organism, How Do Cells Die? Events of apoptosis: •  Cell detaches from its neighbors •  Cuts up its chroma1n into nucleosome ­ sized pieces •  Forms membranous lobes called “blebs” that break into fragments •  Surrounding living cells ingest the remains of the dead cell Figure 11.22 Apoptosis: Programmed Cell Death (A) In a Living Organism, How Do Cells Die? Cell death cycle is controlled by signals: •  Lack of a mito1c signal (growth factor) •  Recogni1on of damaged DNA External signals cause membrane proteins to change shape and ac1vate enzymes called caspases—hydrolyze proteins of membranes. Figure 11.22 Apoptosis: Programmed Cell Death (B) How Does Unregulated Cell Division Lead to Cancer? Cancer cells differ from original cells in two ways: •  Cancer cells lose control over cell division •  They can migrate to other parts of the body How Does Unregulated Cell Division Lead to Cancer? Normal cells divide in response to extracellular signals, like growth factors. Cancer cells don’t respond to these signals, instead growing almost con1nuously. A tumor is a large mass of cells. How Does Unregulated Cell Division Lead to Cancer? Benign tumors resemble the 1ssue they grow from, grow slowly, and remain localized. They are not cancerous but must be removed if they obstruct an organ or func1on. How Does Unregulated Cell Division Lead to Cancer? Malignant tumors do not resemble the 1ssue they grow from and may have irregular structures. Cancer cells can invade surrounding 1ssue and travel through the bloodstream or lymph system. Metastasis, or spreading, can cause organ failure and is hard to treat. Figure 11.23 A Cancer Cell with its Normal Neighbors How Does Unregulated Cell Division Lead to Cancer? Normal posi1ve regulators such as growth factors s1mulate the cell cycle. Normal nega1ve regulators such as RB inhibit the cell cycle. These regulators normally control cell division but in cancer they are abnormal. How Does Unregulated Cell Division Lead to Cancer? Oncogene proteins are posi1ve regulators of cancer cells. Derived from normal regulators that are overac1ve or in excess, such as growth factors or their receptors. Example: An increased number of receptors for HER2 in breast 1ssue may result in rapid cell prolifera1on. Figure 11.24 Molecular Changes in Cancer Cells (A) How Does Unregulated Cell Division Lead to Cancer? Tumor suppressors are nega1ve regulators in both cancer and normal cells, but in cancer cells they are inac1ve. Proteins such as p21, p53, and RB that normally block the cell cycle are tumor suppressors but may be blocked by a virus, such as HPV. Figure 11.24 Molecular Changes in Cancer Cells (B) How Does Unregulated Cell Division Lead to Cancer? Cancer treatment targets the cell cycle and tries to inhibit division. Drugs such as 5 ­flourouracil block thymine, a base of DNA. Taxol interferes with the mito1c spindle. Hercep.n targets only the HER2 growth factor receptor in some breast cancers. Figure 11.25 Cancer Treatment and the Cell Cycle ...
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