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  • A hypothetical sequence for the evolution of mitosis Some unicellular eukaryotic organisms existing today display mechanisms of cell division that appear to be intermediate btwn binary fission as in bacteria (a) and mitosis as it is shown in most other eukaryotes (b-d)

cell cycle cell cycle Presentation Transcript

  • Chapter 12 The Cell Cycle
  • Introduction: Key Roles of Cell Division
    • The ability of organisms to reproduce their kind is one characteristic that best distinguishes living things from nonliving matter.
    • The continuity of life from one cell to another is based on the reproduction of cells via cell division .
    • This division process occurs as part of the cell cycle , the life of a cell from its origin in the division of a parent cell until its own division into two.
  • Cell division requires coordinated division of chromosomes (mitosis) ….. …… and division of the cytoplasm (cytokinesis).
  • Introduction: Key Roles of Cell Division
    • In unicellular organisms, division of one cell reproduces the entire organism i.e. cloning
    • Multicellular organisms depend on cell division for:
      • Development
      • Growth
      • Repair
  • LE 12-2 Reproduction 100 µm Tissue renewal Growth and development 20 µm 200 µm
  • Cell division results in genetically identical daughter cells
    • Cells duplicate their genetic material before they divide, ensuring that each daughter cell receives an exact copy of the genetic material, DNA
    • A dividing cell duplicates its DNA, allocates the two copies to opposite ends of the cell, and only then splits into daughter cells
  • Cellular Organization of the Genetic Material
    • A cell’s endowment of DNA ( genetic information) is called its genome
    • DNA molecules in a cell are packaged into units called chromosomes
      • Every eukaryotic species has a characteristic number of chromosomes in the nucleus.
      • Human somatic cells (body cells) have 46 chromosomes, called the diploid number or 2 n
    • Human gametes, sperm or egg, have 23 chromosomes, or half the diploid number ( n; haploid )
  • Chromosome Anatomy
    • Eukaryotic chromosomes consist of chromatin, a complex of DNA and proteins that condenses during cell division
    • In preparation for cell division, DNA is replicated and the chromosomes condense
    • Each duplicated chromosome consists of two sister chromatids which contain identical copies of the chromosome’s DNA.
    • As they condense, the region where the strands connect shrinks to form a narrow site called the centromere .
  • LE 12-3 25 µm 1888 W. Waldeyer was the first to introduce the term chromosome meaning “ colored body”.
    • Eukaryotic cell division consists of 2 phases:
      • Mitosis (karyokinesis), division of the nucleus
      • Cytokinesis, division of the cytoplasm
    • Gametes are produced by a variation of cell division called meiosis
    • Meiosis yields non-identical daughter cells that have only one set of chromosomes, half as many as the parent cell
    Cell Division
  • M phase alternates with Interphase
    • In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis
    • To Flemming, it appeared that the cell simply grew larger between one cell division and the next
    • Today we know that many critical events occur during this stage in a cell’s life
    • Mitosis =Greek for “ thread ”
  • Phases of the Cell Cycle
    • The cell cycle consists of
      • Mitotic (M) phase (mitosis and cytokinesis)
      • Interphase (cell growth and copying of chromosomes in preparation for cell division)
    • Interphase (about 90% of the cell cycle) can be divided into subphases:
      • G 1 phase (“first gap”)
      • S phase (“synthesis”)
      • G 2 phase (“second gap”)
  • Cell Cycle next  
  • Overview: Phases of Mitosis
    • Mitosis is conventionally divided into five phases:
      • Prophase
      • Prometaphase
      • Metaphase
      • Anaphase
      • Telophase
    • Cytokinesis is well underway by late telophase
    next  
    • Stages of Mitosis- pics *  Sumanas , Inc . animation - Mitosis
    • Prophase - chromatin condenses
    • into chromosomes    
    • Prometaphase - chromosome MT's attach 
    • to kinetochores each homolog has 2 chromatids fig 12.6 *    
    • Metaphase - chromosomes align at equator homologs                               align independently of each other fig 12.6 *
    • Anaphase - MT attached to kinetochore; chromatids  
    • are pulled apart & poles move apart  fig12.8 *
    • Telophase - chromosomes at opposite poles;                                       daughter cells form by cytokinesis  onion root tip cells *
    •              
    • next  
    •         
    •    
  • Video: Animal Mitosis Video: Sea Urchin (time lapse) Animation: Mitosis (All Phases ) Animation: Mitosis Overview Animation: Late Interphase Animation: Prophase Animation: Prometaphase Animation: Metaphase Animation: Anaphase Animation: Telophase Mitotic Animations and Videos
  • The Mitotic Spindle: A Closer Look
    • The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis
    • Assembly of spindle microtubules begins in the centrosome or MOC ( microtubule organizing center )
    • The centrosome, contains a pair of centrioles, replicates, forming two centrosomes; migrate to opposite ends of the cell, as spindle microtubules grow out from them
    • An aster (a radial array of short microtubules) extends from each centrosome
    • The spindle includes the centrosomes, the spindle microtubules, and the asters
    • Some spindle microtubules attach to a structure the kinetochores of chromosomes and move the chromosomes to the metaphase plate
    The Mitotic Spindle: A Closer Look
  • LE 12-7 Microtubules Chromosomes Sister chromatids Aster Centrosome Metaphase plate Kineto- chores Kinetochore microtubules 0.5 µm Overlapping nonkinetochore microtubules 1 µm Centrosome The Mitotic Spindle: A Closer Look
    • In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell
    • The microtubules shorten by depolymerizing tubulin subunits at their kinetochore ends
    The Mitotic Spindle: A Closer Look
  • Chromosome movement Microtubule Motor protein Chromosome Kinetochore Tubulin subunits What is happening at the kinetochore? The kinetochore motor proteins detach and reattach to the kinetochore microtubule, this causes the microtubule to shorten (depolymerize) and thus moving the chromosome.
    • Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell
    • In telophase, genetically identical daughter nuclei form at opposite ends of the cell
    The Mitotic Spindle: A Closer Look
  • Cytokinesis: A Closer Look
    • In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow
    • In plant cells, a cell plate forms during cytokinesis
    Activity Animation: Cytokinesis
  • LE 12-9a Cleavage furrow 100 µm Contractile ring of microfilaments Daughter cells Cleavage of an animal cell (SEM)
  • LE 12-9b 1 µm Daughter cells Cell plate formation in a plant cell (TEM) New cell wall Cell plate Wall of parent cell Vesicles forming cell plate
  • LE 12-10 Nucleus Cell plate Chromosomes Nucleolus Chromatin condensing 10 µm Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is starting to form. Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelope will fragment. Metaphase. The spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate. Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of the cell as their kinetochore micro- tubules shorten. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divide the cytoplasm in two, is growing toward the perimeter of the parent cell.
  • Binary Fission
    • Prokaryotes (bacteria and archaea) reproduce by a type of asexual reproduction called binary fission
    • In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart
  • Origin of replication Cell wall Plasma membrane Bacterial chromosome E. coli cell Two copies of origin Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Binary Fission
  • LE 12-11_2 Origin of replication Cell wall Plasma membrane Bacterial chromosome E. coli cell Two copies of origin Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Replication continues. One copy of the origin is now at each end of the cell. Origin Origin
  • LE 12-11_3 Origin of replication Cell wall Plasma membrane Bacterial chromosome E. coli cell Two copies of origin Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Replication continues. One copy of the origin is now at each end of the cell. Origin Origin Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. Two daughter cells result.
  • The Evolution of Mitosis
    • Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission (or “division in half”)
    • Process does not involve mitosis
    • Certain protists exhibit types of cell division that seem intermediate between binary fission and mitosis.
    • Evidence that modern day mitosis evolved from bacterial binary fission lies in the fact that similar bacterial proteins are related to eukaryotic proteins and function to support mitosis.
  • LE 12-12 Bacterial chromosome Chromosomes Microtubules Prokaryotes Dinoflagellates Intact nuclear envelope Kinetochore microtubules Kinetochore microtubules Intact nuclear envelope Diatoms and yeasts Centrosome Most eukaryotes Fragments of nuclear envelope
  • The cell cycle is regulated by a molecular control system at several points
    • The frequency of cell division varies with the type of cell
    • These cell cycle differences result from regulation at the molecular level
  • Evidence for Cytoplasmic Signals
    • The cell cycle appears to be driven by specific chemical signals present in the cytoplasm
    • Cell fusion experiments identified the existence of a molecular cell cycle switch in cells
    • Evidence for this hypothesis comes from 1970’s experiments in which cultured mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei  the hybrid cell is a heterokaryon
    • Which nucleus controlled the cell cycle?
  • The Rao Johnson Experiment Experiment 1 Experiment 2 S S S G 1 G 1 M M M When a cell in the M phase was fused with a cell in G 1 , the G 1 cell immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. Something in M phase induced interphase cells to divide. When a cell in the S phase was fused with a cell in G 1 , the G 1 cell immediately entered the S phase—DNA was synthesized. S cells contained something that induced regulation in G 1 cells.
  • Conclusion:
    • There are factors that can promote S or M phase. The S phase promoting factor only works on G1 nuclei. The M phase promoter works on everything.
    • In 1971 this M phase promoter from the cytoplasm of M phase Xenopus eggs was identified.
    • The M phase protein called MPF (maturation promoting factor) induced immature egg cells to enter M phase.
  • African clawed frog
    • Xenopus laevis popular organism due to large oocytes.
  • Conclusions from Xenopus experiments
    • MPF induces all eukaryotic cells to undergo mitosis;
    • MPF is a dimer, composed of a protein kinase (Cdk-cyclin dependent kinase) and a cyclin
    • Cdk is an enzyme that phosphorylates a protein
    • Cyclin is a protein that attaches to and activates the Cdk molecule.
    • Regulated by " Growth Factors " (GF)- intercellular signals that trigger cells to pass from G 1 checkpoint
    • MPF - mitotic promoting factor- complex * of two proteins:  cdk + cyclin
    • MPF is a kinase enzyme, switches on/off target cell cycle  proteins by phosphorylating them.....        inactive cycle protein  ------------->active-P                              ATP  ADP
    • MPF promotes entrance into mitosis from the G 2 phase by phosphorylating multiple proteins during mitosis including one that leads to destruction of cyclin itself     MPF   cdk - a cell division control protein - cyclin dependent kinase;                      active only when bound to cyclin ;              cyclin -  a protein whose amount varies cyclically * ;                        when in high concentrations * , binds to cdk makes MPF...                    [cyclin + cdk = MPF]..  favors Mitosis GF regulated at critical points...   Cell cycle checkpoints  
    Control of Cell Division and the Cell Cycle 2001 Nobel prize
  • The Cell Cycle Control System
    • The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock
    • The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received
    • For many cells, the G 1 checkpoint seems to be the most important one
    • If a cell receives a go-ahead signal at the G 1 checkpoint, it will usually complete the S, G 2 , and M phases and divide
    • If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G 0 phase
    The Cell Cycle Control System
  • LE 12-15 G 1 G 1 checkpoint G 1 G 0 If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. If a cell does not receive a go-ahead signal at the G 1 checkpoint, the cell exits the cell cycle and goes into G 0 , a nondividing state.
  • Stop and Go Signs: Internal and External Signals at the Checkpoints
    • An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase
    • Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide
    • For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture
  • LE 12-17 Petri plate Scalpels Without PDGF With PDGF Without PDGF With PDGF 10 mm
    • Another example of external signals is density-dependent inhibition, in which crowded cells stop dividing
    • Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide
    Stop and Go Signs: Internal and External Signals at the Checkpoints
  • LE 12-18a Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). 25 µm Normal mammalian cells
  • Cancer cells escape cell cycle controls
    • Cancer cells divide excessively and invade other tissues because they are free of the body’s control mechanisms.
      • Cancer cells do not stop dividing when growth factors are depleted either because they manufacture their own, have an abnormality in the signaling pathway, or have a problem in the cell cycle control system.
    • If and when cancer cells stop dividing, they do so at random points, not at the normal checkpoints in the cell cycle.
  • LE 12-18b Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. Cancer cells 25 µm
  • Loss of Cell Cycle Controls =Cancer Cells
    • Cancer cells do not respond normally to the body’s control mechanisms
    • Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue
    • If abnormal cells remain at the original site, the lump is called a benign tumor
    • Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form secondary tumors
  • Cancer cells escape cell cycle controls
    • Cancer cells may divide indefinitely if they have a continual supply of nutrients.
      • In contrast, nearly all mammalian cells divide 20 to 50 times under culture conditions before they stop, age, and die.
      • Cancer cells may be “immortal”.
        • Cells (HeLa) from a tumor removed from a woman ( He nrietta La cks) in 1951 are still reproducing in culture.
  • Cancer cell Blood vessel Lymph vessel Tumor Glandular tissue Metastatic tumor A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue. Cancer cells spread through lymph and blood vessels to other parts of the body. A small percentage of cancer cells may survive and establish a new tumor in another part of the body. Cancer
  • Chapter 12 The Cell Cycle THE END!