Chapter 10 biology .pptx

Because learning changes everything. Chapter 10 How Cells Divide BIOLOGY Thirteenth Edition Raven, Johnson, Mason, Losos, Duncan © 2023 McGraw Hill, LLC. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior w...

Because learning changes everything. Chapter 10 How Cells Divide BIOLOGY Thirteenth Edition Raven, Johnson, Mason, Losos, Duncan © 2023 McGraw Hill, LLC. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw Hill, LLC. ® Lecture Outline 10.1 Bacterial Cell Division 10.2 Eukaryotic Chromosomes 10.3 Overview of the Eukaryotic Cell Cycle 10.4 Interphase: Preparation for Mitosis 10.5 M Phase: Chromosome Segregation and the Division of Cytoplasmic Contents 10.6 Control of the Cell Cycle 10.7 Genetics of Cancer Stem Jems/Science Source © McGraw Hill, LLC 2 Bacterial Cell Division Bacteria divide by binary fission • No sexual life cycle. • Reproduction is clonal. Single, circular bacterial chromosome is replicated Replication begins at the origin of replication and proceeds in two directions to site of termination New chromosomes are partitioned to opposite ends of the cell Septum forms to divide the cell into two cells © McGraw Hill, LLC 3 Binary Fission Figure 10.1,1-3 © McGraw Hill, LLC Access the text alternative for slide images. 4 Binary Fission: Septation and Division Figure 10.1,4-5 © McGraw Hill, LLC Access the text alternative for slide images. 5 Septation Courtesy of William Margolin • • • • • Production of septum separates cell’s other components Begins with formation of ring of FtsZ proteins Accumulation of other proteins follow Structure contracts radially to pinch cell in two FtsZ protein found in most prokaryotes Figure 10.2 © McGraw Hill, LLC Access the text alternative for slide images. 6 FtsZ • FtsZ protein has a structure similar to eukaryotic tubulin • Role of FtsZ in bacterial division is very different from the role of tubulin in mitosis in eukaryotes • Different protein assemblies are utilized in cell division by different organisms © McGraw Hill, LLC 7 Protein Assemblies Across Organisms Figure 10.3 © McGraw Hill, LLC Access the text alternative for slide images. 8 Eukaryotic Chromosomes Eukaryotes typically have 10 to 50 chromosomes in their body (somatic) cells Humans have 46 chromosomes in 23 nearly identical pairs • Additional/missing chromosomes usually fatal. Figure 10.4 © McGraw Hill, LLC Biophoto Associates/Science Source 9 Karyotype Particular array of chromosomes in an individual organism • Arranged according to size, staining properties, location of centromere, etc. Humans are diploid (2n) • Two complete sets of chromosomes. • 46 total chromosomes. Haploid (n) • One set of chromosomes. • 23 in humans. Pair of chromosomes are homologous • Each one is a homologue. © McGraw Hill, LLC 10 Human Karyotype CNRI/Science Source Figure 10.5 © McGraw Hill, LLC Access the text alternative for slide images. 11 DNA Is Organized into Chromatin The precise structure of chromosomes, and how they change over the cell cycle, is not fully understood. Chromosomes are composed of chromatin – a complex of D NA and protein • 40% DNA • 60% protein © McGraw Hill, LLC 12 Chromosomes RNA is also associated with chromosomes during RNA synthesis DNA of a single chromosome is one long continuous molecule Typical human chromosome 140 million nucleotides long • Average length is 4.3cm • Is compacted to varying degrees within a cell © McGraw Hill, LLC 13 Nucleosomes A chromosome is a complex of DNA and histone proteins. • Histone is positively charged • DNA is negatively charged Four primary histones: • H2A, H2B, H3, H4 DNA 147 bp long is coiled 1.7 turns around 8 histones • Diameter is 10nm Linker DNA of 20 to 80 bp separates nucleosomes • “Beads on a string” © McGraw Hill, LLC 14 H1 An additional histone Can interact with linker DNA Has a role in the formation of 30nm DNA • Forms from DNA with nucleosomes incubated in low salt conditions with H1 • May not exist in cells © McGraw Hill, LLC 15 Chromatin Is Spatially Organized Chromatin is organized into territories. • Territories contain individual chromosomes. Compartments exist within each chromosome. Formed by TADs Don W. Fawcett/Science Source Access the text alternative for slide images. © McGraw Hill, LLC 16 TADs Topologically associated domains Loops of DNA in nucleosomes Anchored by 2 proteins • CTCF: a DNA-binding protein • Cohesions Organization may affect the control of gene expression © McGraw Hill, LLC 17 Heterochromatin and Euchromatin Domains that differ in organization in compartments and TADs • Heterochromatin • Not active • Euchromatin • Active © McGraw Hill, LLC 18 Eukaryotic Chromosome Organization Don W. Fawcett/Science Source Figure 10.6 © McGraw Hill, LLC Access the text alternative for slide images. 19 Chromosomal Condensation Condensation varies throughout the cell cycle. Familiar X-shaped mitotic chromosomes are arranged around scaffold of protein to achieve maximum compaction TADs disappear during prophase • More regular interactions occur • SMC (Structural maintenance of chromosome) proteins interact with the DNA • Condensin replaces cohesion DNA appears to be more fluid © McGraw Hill, LLC 20 One New Model Cohesion proteins are organized along the scaffold ATP is used to form regular loops of DNA in nucleosomes • Further twisted to compact the loops DNA is wrapped into nucleosomes Interactions of linker histones, and the nucleosomes themselves can change the density of the “liquid DNA”. © McGraw Hill, LLC 21 Replication Prior to replication, each chromosome composed of a single DNA molecule After replication, each chromosome composed of 2 identical DNA molecules • Held together by cohesin proteins. Visible as 2 strands connected in middle as chromosome is more condensed • One chromosome composed of 2 sister chromatids. © McGraw Hill, LLC 22 Homologous versus Duplicated Chromosomes Figure 10.7 © McGraw Hill, LLC Access the text alternative for slide images. 23 Eukaryotic Cell Cycle 1. G1 (gap phase 1) • Primary growth phase, longest phase 2. S (synthesis) Interphase • Replication of DNA 3. G2 (gap phase 2) • Organelles replicate, microtubules organize 4. M (mitosis) • Subdivided into 5 phases. 5. C (cytokinesis) • Separation of 2 new cells. Access the text alternative for slide images. © McGraw Hill, LLC 24 Duration Time it takes to complete a cell cycle varies greatly Fruit fly embryos = 8 minutes Mature cells take longer to grow • Typical mammalian cell takes 24 hours. • Liver cell takes more than a year. Growth occurs during G1, G2, and S phases • M phase takes about an hour. Most variation in length of G1 • Resting phase G0 – cells spend more or less time here. © McGraw Hill, LLC 25 Cell Cycle Figure 10.8 © McGraw Hill, LLC Access the text alternative for slide images. 26 Interphase G1, S, and G2 phases • G1 – cells undergo major portion of growth. • S – replicate DNA. • G2 – chromosomes coil more tightly using motor proteins; centrioles replicate; tubulin synthesis. Centromere – point of constriction • Kinetochore – attachment site for microtubules. • Each sister chromatid has a centromere. • Chromatids stay attached at centromere by cohesin. • Replaced by condensin in multicellular animals. © McGraw Hill, LLC 27 Kinetochores Figure 10.9 © McGraw Hill, LLC Access the text alternative for slide images. 28 Protein Found at the Centromere Courtesy of Peter Lenart and Jan-Michael Peters Access the text alternative for slide images. © McGraw Hill, LLC 29 Interphase Cellular Organization Andrew S. Bajer, University of Oregon Figure 10.11 © McGraw Hill, LLC Access the text alternative for slide images. 30 M phase Mitosis is divided into five phases: 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase © McGraw Hill, LLC 31 Prophase Individual condensed chromosomes first become visible with the light microscope • Condensation continues throughout prophase. Spindle apparatus assembles • Two centrioles move to opposite poles forming spindle apparatus (no centrioles in plants). • Asters – radial array of microtubules in animals (not plants). Nuclear envelope breaks down © McGraw Hill, LLC 32 Prophase Cellular Organization Andrew S. Bajer, University of Oregon Figure 10.11 © McGraw Hill, LLC Access the text alternative for slide images. 33 Prometaphase Transition occurs after disassembly of nuclear envelope Microtubule attachment • 2nd group grows from poles and attaches to kinetochores. • Each sister chromatid connected to opposite poles. Chromosomes begin to move to center of cell – congression • Assembly and disassembly of microtubules. • Motor proteins at kinetochores. © McGraw Hill, LLC 34 Prometaphase Cellular Organization Andrew S. Bajer, University of Oregon Figure 10.11 © McGraw Hill, LLC Access the text alternative for slide images. 35 Metaphase Alignment of chromosomes along metaphase plate • Not an actual structure. • Future axis of cell division. Figure 10.12 © McGraw Hill, LLC Andrew S. Bajer, University of Oregon 36 Metaphase cellular organization Andrew S. Bajer, University of Oregon Figure 10.11 © McGraw Hill, LLC Access the text alternative for slide images. 37 Anaphase Begins when centromeres split Key event is removal of cohesin proteins from all chromosomes Sister chromatids pulled to opposite poles Two forms of movements: 1. Anaphase A – kinetochores pulled toward poles 2. Anaphase B – poles move apart Dr. Jeremy Pickett-Heaps Access the text alternative for slide images. © McGraw Hill, LLC 38 Anaphase Cellular Organization Andrew S. Bajer, University of Oregon Figure 10.11 © McGraw Hill, LLC Access the text alternative for slide images. 39 Telophase Spindle apparatus disassembles Nuclear envelope forms around each set of sister chromatids • Now called chromosomes. Chromosomes begin to uncoil Nucleolus reappears in each new nucleus © McGraw Hill, LLC 40 Telophase Cellular Organization Andrew S. Bajer, University of Oregon Figure 10.11 © McGraw Hill, LLC Access the text alternative for slide images. 41 Cytokinesis • Cleavage of the cell into equal halves • Animal cells – constriction of actin filaments produces a cleavage furrow • Plant cells – cell plate forms between the nuclei • Fungi and some protists – nuclear membrane does not dissolve; mitosis occurs within the nucleus; division of the nucleus occurs with cytokinesis © McGraw Hill, LLC 42 Animal Cell Cytokinesis (a) Don W. Fawcett/Science Source; (b) Guenter Albrecht-Buehler, Northwestern University, Chicago Figure 10.14 © McGraw Hill, LLC Access the text alternative for slide images. 43 Plant Cell Cytokinesis ©Biophoto Associates/Science Source Figure 10.15 © McGraw Hill, LLC Access the text alternative for slide images. 44 Control of the Cell Cycle Cell cycle has two irreversible points: 1. Replication of genetic material 2. Separation of the sister chromatids Cell cycle can be put on hold at specific points called checkpoints • Process is checked for accuracy and can be halted if there are errors. • Allows cell to respond to internal and external signals. © McGraw Hill, LLC 45 Cell Cycle Control Factors – MPF • Maturation-promoting factor (MPF) discovered in frog oocytes • Cytoplasm containing MPF can induce cell division • MPF activity varies throughout the cell cycle • MPF enzymatic activity involved the phosphorylation of proteins © McGraw Hill, LLC 46 Cell Cycle Control Factors - Cyclins • Research in sea urchin embryos discovered proteins that are produced in synchrony with the cell cycle • Named cyclin • Two forms – one that peaks at G1/S, another that peaks at G2/M © McGraw Hill, LLC 47 Cell Cycle Control Factors – cdc2 Yeast mutants that halted during cell division were used to identify genes necessary for cell cycle progression In yeast there were two critical control points: • commitment to DNA synthesis (“START”) • commitment to mitosis cdc2 gene is critical for passing both boundaries © McGraw Hill, LLC 48 MPF is Cyclin Plus cdc2 • Protein encoded by cdc2 was shown to be a kinase • MPF was shown to be composed of a cyclin and cdc2 kinase • cdc2 was first identified cyclin-dependent kinase (cdk) • Cdks are the key positive drivers of the cell cycle © McGraw Hill, LLC 49 Three Checkpoints 1. G1/S checkpoint • • Cell “decides” to divide. Primary point for external signal influence. 2. G2/M checkpoint • • Cell makes a commitment to mitosis. Assesses success of DNA replication. 3. Late metaphase (spindle) checkpoint • © McGraw Hill, LLC Cell ensures that all chromosomes are attached to the spindle. 50 Cell Cycle Control Figure 10.18 © McGraw Hill, LLC Access the text alternative for slide images. 51 Cyclin-Dependent Kinases (Cdks) • Enzymes that phosphorylate proteins • Primary mechanism of cell cycle control • Cdks partner with different cyclins at different points in the cell cycle © McGraw Hill, LLC 52 Cdk-Cyclin Complex Cdk – cyclin complex • Also called mitosis-promoting factor (M PF). Activity of Cdk is also controlled by the pattern of phosphorylation • Phosphorylation at one site (red) inactivates Cdk. • Phosphorylation at another site (green) activates Cdk. Figure 10.19 © McGraw Hill, LLC Access the text alternative for slide images. 53 MPF • Once thought that MPF was controlled solely by the level of the M phase-specific cyclins • Although M phase cyclin is necessary for MPF function, activity is controlled by inhibitory phosphorylation of the kinase component, Cdc2 • Damage to DNA acts through a complex pathway to tip the balance toward the inhibitory phosphorylation of MPF © McGraw Hill, LLC 54 Anaphase-Promoting Complex (APC) • Also called cyclosome (APC/C) • At the spindle checkpoint, presence of all chromosomes at the metaphase plate and the tension on the microtubules between opposite poles are both important • Function of the APC/C is to trigger anaphase itself • Marks securin for destruction; no inhibition of separase; separase destroys cohesion © McGraw Hill, LLC 55 Control in Multicellular Eukaryotes • Multiple Cdks control the cycle as opposed to the single Cdk in yeasts • Animal cells respond to a greater variety of external signals than do yeasts, which primarily respond to signals necessary for mating • More complex controls allow the integration of more input into control of the cycle © McGraw Hill, LLC 56 Yeast Cell Cycle Control Figure 10.20 © McGraw Hill, LLC Access the text alternative for slide images. 57 Growth Factors • Act by triggering intracellular signaling systems • Platelet-derived growth factor (PDGF) one of the first growth factors to be identified • PDGF receptor is a receptor tyrosine kinase (RTK) that initiates a MAP kinase cascade to stimulate cell division • Growth factors can override cellular controls that otherwise inhibit cell division © McGraw Hill, LLC 58 Cell Proliferation Figure 10.21 © McGraw Hill, LLC Access the text alternative for slide images. 59 Cancer Unrestrained, uncontrolled growth of cells Failure of cell cycle control Two kinds of genes can disturb the cell cycle when they are mutated: 1. Tumor-suppressor genes 2. Proto-oncogenes © McGraw Hill, LLC 60 Proto-oncogenes Normal cellular genes that become oncogenes when mutated • Oncogenes can cause cancer. Some encode receptors for growth factors • If receptor is mutated in “on,” cell no longer depends on growth factors. Some encode signal transduction proteins Only one copy of a proto-oncogene needs to undergo this mutation for uncontrolled division to take place © McGraw Hill, LLC 61 Tumor-suppressor genes p53 gene and many others Both copies of a tumor-suppressor gene must lose function for the cancerous phenotype to develop First tumor-suppressor identified was the retinoblastoma susceptibility gene (Rb) • Predisposes individuals for a rare form of cancer that affects the retina of the eye. © McGraw Hill, LLC 62 Retino-blastoma Susceptibility Gene (Rb) Inheriting a single mutant copy of Rb means the individual has only one “good” copy left • During the hundreds of thousands of divisions that occur to produce the retina, any error that damages the remaining good copy leads to a cancerous cell. • Single cancerous cell in the retina then leads to the formation of a retinoblastoma tumor. Rb protein integrates signals from growth factors • Role to bind important regulatory proteins and prevent stimulation of cyclin or Cdk production. © McGraw Hill, LLC 63 p53 gene p53 plays a key role in G1 checkpoint p53 protein monitors integrity of DNA • If DNA damaged, cell division halted and repair enzymes stimulated. • If DNA damage is irreparable, p53 directs cell to kill itself. Prevent the development of many mutated cells p53 is absent or damaged in many cancerous cells © McGraw Hill, LLC 64 Proteins Associated with Human Cancer Figure 10.23 © McGraw Hill, LLC Access the text alternative for slide images. 65 Whole-Genome Sequencing This is shedding light on cancer genetics. Previous model of a linear progression of mutations may be simplistic. Cells within tumors are sequenced and compared to normal cells. Has led to the idea of • Mountain genes: mutated in a significant number of tumors • Hill genes: less frequently mutated © McGraw Hill, LLC 66 New Categories of Genes in the Cancer Genome These genes probably act by increasing the number of mutations, or changes in gene expression in a tumor. Categories include: • DNA repair • mRNA splicing • Chromosome architecture © McGraw Hill, LLC 67 Spectra of Mutations Different cancers have different spectra of mutated genes. Important in • Diagnosis • Specific therapies SMGs: significantly modified genes Associated with specific tumor types Data can be combined with • how a patient’s genotype affects the growth of cancer • the drugs that may be effective in treatment © McGraw Hill, LLC 68 Heterogeneity in Tumor Cells Revealed via sequencing Tumors are NOT clones of a single cell. Within a single tumor, there is variation in • Amount of chromosomal alterations • Kind of chromosomal alterations This has uncovered new mechanisms that damage genes and chromosomes. © McGraw Hill, LLC 69 End of Main Content Because learning changes everything. www.mheducation.com © 2023 McGraw Hill, LLC. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw Hill, LLC. ®