Biology Sylvia S. Mader Michael Windelspecht Chapter 9 The Cell Cycle and Cellular Reproduction Lecture Outline Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. See separate FlexArt PowerPoint slides for all figures and tables pre-inserted into PowerPoint without notes. 1

Outline 9.1 The Cell Cycle 9.2 Mitosis and Cytokinesis 9.3 The Cell Cycle and Cancer 9.4 Prokaryotic Cell Division 2

9.1 The Cell Cycle cell cycle division resulting in 2 daughter cells prior to division:  cell grows larger  # of organelles doubles  DNA is replicated 2 major stages:  Interphase (includes several stages)  Mitotic Stage (mitosis & cytokinesis) 3

The Cell Cycle 4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. G 1 (growth) G0G0 G 2 checkpoint Mitosis checkpoint. Mitosis will occur if DNA has replicated properly. Apoptosis will occur if the DNA is damaged and cannot be repaired. S (growth and DNA replication) M Cytokinesis T elophase Anaphase Metaphase Late prophase Prophase Interphase G1 checkpoint Cell cycle main checkpoint. If DNA is damaged, apoptosis will occur. Otherwise, the cell is committed to divide when growth signals are present and nutrients are available. M checkpoint Spindle assembly checkpoint. Mitosis will not continue if chromosomes are not properly aligned. M G2G2 G1G1 G 2 (growth and final preparations for division)

The Cell Cycle Interphase  Most of the cell cycle  Cell performs usual functions  Time varies by cell type  Nerve & muscle cells do not complete the cell cycle (remain in the G 0 stage) 5

The Cell Cycle Interphase consists of: G 1, S, and G 2 phases  G 1 Phase: Recovery from previous division doubles organelles Grows accumulates materials for DNA synthesis  S Phase: DNA replication Proteins associated with DNA are synthesized Chromosomes start w/ 1 chromatid each Chromosomes leave w/ 2 identical chromatids (sister chromatids)  G 2 Phase: Btw DNA replication and onset of mitosis synthesize proteins necessary for division 6

The Cell Cycle M (Mitotic) Stage  Includes: Mitosis –Nuclear division –Daughter chromosomes are distributed by the mitotic spindle to two daughter nuclei Cytokinesis –Division of the cytoplasm  Results in 2 genetically identical daughter cells 7

The Cell Cycle controlled by internal/external signals Signal- molecule stimulates or inhibits metabolic events  Internal signals Cyclins: increase/ decrease during cell cycle W/o cyclins, cell cycle stops at G 1, M or G 2 (checkpoints) Allows time for damage repair 8

The Cell Cycle Apoptosis- programmed cell death  fragmenting of nucleus,  blistering of plasma membrane  engulfing of cell fragments  caused by enzymes called caspases. Mitosis and apoptosis are opposing forces 9

Apoptosis 10 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. apoptotic cell cell fragment DNA fragment Cell rounds up, and nucleus collapses. Chromatin condenses, and nucleus fragments. Plasma membrane blisters, and blebs form. Cell fragments contain DNA fragments. blebs Courtesy Douglas R. Green/LaJolla Institute for Allergy and Immunology

The Cell Cycle: Apoptosis  Caspases are kept in check by inhibitors Can be unleashed by internal or external signals  Signal protein p53 Stops the cell cycle at G 1 when DNA is damaged attempts to repair DNA –If successful, the cycle continues to mitosis –If not, apoptosis is initiated 11

Regulation at the G1 Checkpoint 12 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. a. P P RB protein RB protein E2F CDK not present E2F not released released E2F E2F binds to DNA. DNA cell cycle proteins phosphorylated RB CDK present b. P P P P breakdown of p53 no DNA damage DNA damage phosphorylated p53 DNA repair proteins apoptosis p53 binds to DNA. DNA p53

9.2 Mitosis and Cytokinesis DNA is v. long  DNA + histones = chromatin  condenses (coils) into visible chromosomes before mitosis 13

Mitosis and Cytokinesis diploid (2n)= 2 sets of chromosomes  Humans diploid 2n= 46 (2 sets of 23 chromosomes)  Body cells haploid (n)= 1 set of chromosomes Sex cells (sperm & eggs) are haploid (n) Humans n= 23 –One set from father (paternal) –One set from mother (maternal) 14 Bee Pancakes

15 Diploid Chromosome Numbers of Some Eukaryotes

Mitosis and Cytokinesis End of S phase:  chromosomes duplicated  Sister chromatids (two strands of genetically identical chromosomes) Attached at centromere Centrosome- outside nucleus  microtubule organizing center (animal cells)  Organizes mitotic spindle (bundles of microtubles)  contains 2 centrioles 16

Duplicated Chromosomes 17 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. centromere sister chromatids one chromatid a. b. kinetochore 9,850 © Andrew Syred/Photo Researchers, Inc.

Mitosis and Cytokinesis 1.Prophase  Chromatin condenses See chromosomes w/ microscope  Nucleolus disappears  Nuclear envelope disintegrates  Spindle assemble  centrosomes move away from each other  Microtubules form star- like arrays- asters 18

Phases of Mitosis in Animal and Plant Cells Animal cell(Early prophase): © Ed Reschke; Plant cell(Early prophase): © Ed Reschke Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Early Prophase aster 20 µm 25 µm MITOSIS Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting. chromatin condenses nucleolus disappears nuclear envelope fragments Animal Cell at Interphase centrosome has centrioles centrosome lacks centrioles Plant Cell at Interphase

Phases of Mitosis in Animal and Plant Cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Animal cell(Early prophase, Prophase): © Ed Reschke; Plant cell(Early prophase): © Ed Reschke; Plant cell(Prophase): © R. Calentine/Visuals Unlimited Prophase spindle fibers forming centromere aster chromosomescell wall 20 µm 6.2 µm25 µm Prophase Nucleolus has disappeared, and duplicated chromosomes are visible. Centrosomes begin moving apart, and spindle is in process of forming. MITOSIS centrosome lacks centrioles Animal Cell at Interphase centrosome has centrioles nuclear envelope fragments chromatin condenses nucleolus disappears Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting. duplicated chromosome Plant Cell at Interphase

Mitosis and Cytokinesis 2.Prometaphase  Centromere develops 2 kinetochores 21

Phases of Mitosis in Animal and Plant Cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Animal cell(Early prophase, Prophase, Metaphase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.; Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase): © R. Calentine/Visuals Unlimited Prometaphase centromere spindle pole aster kinetochore polar spindle fiber chromosomescell wall 20 µm 6.2 µm25 µm20 µm 9 µm Prometaphase The kinetochore of each chromatid is attached to a kinetochore spindle fiber. Polar spindle fibers stretch from each spindle pole and overlap. centrosome has centrioles Animal Cell at Interphase nuclear envelope fragments chromatin condenses nucleolus disappears spindle fibers forming Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting. Prophase Nucleolus has disappeared, and duplicated chromosomes are visible. Centrosomes begin moving apart, and spindle is in process of forming. kinetochore spindle fiber duplicated chromosome spindle pole lacks centrioles and aster Plant Cell at Interphase centrosome lacks centrioles MITOSIS

Mitosis and Cytokinesis 3. Metaphase  Chromosomes pulled at kinetochore  align on equatorial plane Metaphase plate - plane for cell division 23

Phases of Mitosis in Animal and Plant Cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Animal cell(Early prophase, Prophase, Metaphase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.; Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase): © R. Calentine/Visuals Unlimited duplicated chromosome centromere aster kinetochore polar spindle fiber chromosomescell wall 20 µm 6.2 µm25 µm20 µm 9 µm spindle fibers 20 µm 6.2 µm Metaphase Centromeres of duplicated chromosomes are aligned at the metaphase plate (center of fully formed spindle). Kinetochore spindle fibers attached to the sister chromatids come from opposite spindle poles. centrosome has centrioles Animal Cell at Interphase nuclear envelope fragments nucleolus disappears chromatin condenses centrosome lacks centrioles Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting. Prophase Nucleolus has disappeared, and duplicated chromosomes are visible. Centrosomes begin moving apart, and spindle is in process of forming. Prometaphase The kinetochore of each chromatid is attached to a kinetochore spindle fiber. Polar spindle fibers stretch from each spindle pole and overlap. Metaphase kinetochore spindle fiber chromosomes at metaphase plate spindle pole kinetochore spindle fiber spindle fibers forming Plant Cell at Interphase spindle pole lacks centrioles and aster MITOSIS 20 µm

25 Mitosis and Cytokinesis 4. Anaphase Centromere dissolves, releasing sister chromatids Sister chromatids separate to opposite poles –Now called daughter chromosomes

Phases of Mitosis in Animal and Plant Cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Animal cell(Early prophase, Prophase, Metaphase, Anaphase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.; Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase, Anaphase): © R. Calentine/Visuals Unlimited centromere spindle pole aster kinetochore spindle fiber polar spindle fiber chromosomescell wall 20 µm 6.2 µm25 µm20 µm 9 µm daughter chromosome spindle fibers 20 µm 6.2 µm centrosome has centrioles Animal Cell at Interphase nuclear envelope fragments nucleolus disappears chromatin condenses centrosome lacks centrioles Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting. Prophase Nucleolus has disappeared, and duplicated chromosomes are visible. Centrosomes begin moving apart, and spindle is in process of forming. Prometaphase The kinetochore of each chromatid is attached to a kinetochore spindle fiber. Polar spindle fibers stretch from each spindle pole and overlap. Metaphase Centromeres of duplicated chromosomes are aligned at the metaphase plate (center of fully formed spindle). Kinetochore spindle fibers attached to the sister chromatids come from opposite spindle poles. kinetochore spindle fiber Anaphase chromosomes at metaphase plate spindle pole lacks centrioles and aster Plant Cell at Interphase duplicated chromosome spindle fibers forming MITOSIS Anaphase Sister chromatids part and become daughter chromosomes that move toward the spindle poles. In this way, each pole receives the same number and kinds of chromosomes as the parent cell.

Mitosis and Cytokinesis 5.Telophase  Chromosomes begin to uncoil  Spindle disappears  Nucleoli reform  Nuclear envelopes re- form around daughter cells 27

Phases of Mitosis in Animal and Plant Cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. centromere aster kinetochore polar spindle fiber chromosomescell wall 20 µm 6.2 µm25 µm20 µm 9 µm daughter chromosome spindle fiberscell plate 20 µm 16 µm 6.2 µm6.6 µm6.2 µm nucleolus cleavage furrow Telophase Daughter cells are forming as nuclear envelopes and nucleoli reappear. Chromosomes will become indistinct chromatin. centrosome has centrioles Animal Cell at Interphase nuclear envelope fragments chromatin condenses nucleolus disappears centrosome lacks centrioles Plant Cell at Interphase Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting. spindle fibers forming duplicated chromosome kinetochore spindle fiber Prophase Nucleolus has disappeared, and duplicated chromosomes are visible. Centrosomes begin moving apart, and spindle is in process of forming. Prometaphase The kinetochore of each chromatid is attached to a kinetochore spindle fiber. Polar spindle fibers stretch from each spindle pole and overlap. Metaphase Centromeres of duplicated chromosomes are aligned at the metaphase plate (center of fully formed spindle). Kinetochore spindle fibers attached to the sister chromatids come from opposite spindle poles. Anaphase Sister chromatids part and become daughter chromosomes that move toward the spindle poles. In this way, each pole receives the same number and kinds of chromosomes as the parent cell. Telophase spindle pole lacks centrioles and aster spindle pole chromosomes at metaphase plate kinetochore spindle fiber Animal cell(Early prophase, Prophase, Metaphase, Anaphase, Telophase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.; Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase, Anaphase): © R. Calentine/Visuals Unlimited; Plant cell(Telophase): © Jack M. Bostrack/Visuals Unlimited; MITOSIS

Mitosis and Cytokinesis 6.Cytokinesis = division of cytoplasm  Allocates cytoplasm equally to daughter cell  Encloses each cell in plasma membrane  Begins in anaphase  Animal cytokinesis: cleavage furrow appears between daughter cells Formed by contractile ring (actin) Pinches cell in two 29

Cytokinesis in Animal Cells 30 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cleavage furrow Contractile ring X 4,000 (top): © Thomas Deerinck/Visuals Unlimited; (bottom): © SPL/Getty RF

Mitosis and Cytokinesis Plant cytokinesis: formation of a cell plate  cell walls don’t permit furrowing  Many small vesicles  fuse into 1 thin vesicle  cell plate membranes become plasma membrane of daughter cells  The space between the daughter cells becomes filled with the middle lamella 31

Cytokinesis in Plant Cells 32 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. daughter cells nucleoli daughter nucleus cell plate formation daughter nucleus vesicles containing membrane components fusing to form cell plate (left): © B.A. Palevitz and E.H. Newcomb/BPS/Tom Stack & Associates

33 Phases of Mitosis in Animal and Plant Cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Animal cell(Early prophase, Prophase, Metaphase, Anaphase, Telophase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.; Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase, Anaphase): © R. Calentine/Visuals Unlimited; Plant cell(Telophase): © Jack M. Bostrack/Visuals Unlimited; Plant Cell at Interphase centromere aster kinetochore polar spindle fiber chromosomescell wall 25µm centrosome lacks centrioles MITOSIS centrosome has centrioles Animal Cell at Interphase nuclear envelope fragments chromatin condenses nucleolus disappears Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting. Prophase Nucleolus has disappeared, and duplicated chromosomes are visible. Centrosomes begin moving apart, and spindle is in process of forming. Prophase Nucleolus has disappeared, and duplicated chromosomes are visible. Centrosomes begin moving apart, and spindle is in process of forming. 20 µm duplicated chromosome 20 µm spindle fibers forming spindle pole 9 µm kinetochore spindle fiber cleavage furrow spindle fibers 20µm 16µm kinetochore spindle fiber Anaphase Sister chromatids part and become daughter chromosomes that move toward the spindle poles. In this way, each pole receives the same number and kinds of chromosomes as the parent cell. Metaphase Centromeres of duplicated chromosomes are aligned at the metaphase plate (center of fully formed spindle). Kinetochore spindle fibers attached to the sister chromatids come from opposite spindle poles. chromosomes at metaphase plate 6.2µm 20µm 6.2µm spindle pole lacks centrioles and aster Telophase Daughter cells are forming as nuclear envelopes and nucleoli reappear. Chromosomes will become indistinct chromatin. daughter chromosome 20µm nucleolus cell plate 6.6µm

Functions of Mitosis  Permits growth and repair.  Flowering plants: meristematic tissue divides for entire plant life Plant growth  Mammals: Growth of fertilized egg  embryo  fetus Heal cuts / broken bones 34

Phases of Mitosis in Animal and Plant Cells Stem Cells  Retain the ability to divide- can become any type of cell  Blood types  Therapeutic cloning- use stem cells to cure illness  Reproductive cloning- use embryonic stem cells to make new individual 35

Reproductive and Therapeutic Cloning 36 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. remove and discard egg nucleus egg remove G o nucleus G o cells from animal to be cloned egg fuse egg with G o nucleus Implant embryo into surrogate mother Clone is born culture embryonic stem cells nervous blood muscle embryonic stem cells culture fuse egg with G o nucleus remove and discard egg nucleus G o somatic cells remove G o nucleus b. Therapeutic cloning a. Reproductive cloning

9.3 The Cell Cycle and Cancer Tumor- abnormal cell growth  Benign: tumors not cancerous Encapsulated Don’t invade or spread  Malignant: cancerous tumors Not encapsulated Readily invade Metastasis- lodge in distant places mutation of genes regulating cell cycle Development  Gradual, yrs. before detectable 37

The Cell Cycle and Cancer Characteristics  Lack differentiation non-specialized immortal  Abnormal nuclei Enlarged abnormal # of chromosomes extra gene copies  No apoptosis! damaged DNA  apoptosis immune system can trigger apoptosis 38

The Cell Cycle and Cancer Characteristics cont.  Tumor formation lost contact inhibition  Undergo metastasis Tumor fragments  appear in other organs  Undergo angiogenesis Formation of new blood vessels –Brings nutrients & oxygen 39

Progression of Cancer 40 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. primary tumor New mutations arise, and one cell (brown) has the ability to start a tumor. Cancer in situ. The tumor is at its place of origin. One cell (purple) mutates further. Cancer cells now have the ability to invade lymphatic and blood vessels and travel throughout the body. New metastatic tumors are found some distance from the primary tumor. lymphatic vessel blood vessel lymphatic vessel blood vessel

Cancer Cells vs. Normal Cells 41

Origin of Cancer- Mutations  Oncogenes- mutated proto-oncogenes Proto-oncogenes stimulate cell cycle & prevent apoptosis  Tumor suppressor genes inhibit the cell cycle & promote apoptosis  proto-oncogenes & tumor suppressor genes are regulated w/ organism’s growth plan 42

Causes of Cancer 43 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. d: © Biophoto Associates/Photo Researchers, Inc. activated signaling protein growth factor receptor protein signaling protein phosphate b. Effect of growth factor P P P proto-oncogene Codes for a growth factor, a receptor protein, or a signaling protein in a stimulatory pathway. If a proto-oncogene becomes an oncogene, the end result can be active cell division. tumor suppressor gene Codes for a signaling protein in an inhibitory pathway. If a tumor suppressor gene mutates, the end result can be active cell division. c. Stimulatory pathway and inhibitory pathway 1,100X d. Cancerous skin cell gene product promotes cell cycle Stimulatory pathway Inhibitory pathway gene product inhibits cell cycle growth factor Activates signaling proteins in a stimulatory pathway that extends to the nucleus. a. Influences that cause mutated proto-oncogenes (called oncogenes) and mutated tumor suppressor genes Heredity Radiation sources Pesticides and herbicides Viruses oncogene

Origin of Cancer- Mutations  telomeres: end of chromosomes  get shorter each cell division  get very short  cell no longer divide  Telomerase: enzyme that maintains telomere length  Mutations telomerase: Telomeres maintain constant length Allows cancer cells to continually divide 44

9.4 Prokaryotic Cell Division Prokaryotic chromosome:  circular  Folded in nucleoid  1,000 X cell length  Replicated rings attach to the plasma membrane Binary fission: asexual reproduction  Splitting in two  Produces 2 identical daughter cells 45

Binary Fission 46 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. chromosome cell wall plasma membrane cytoplasm SEM2,345X 1. Attachment of chromosome to a special plasma membrane site indicates that this bacterium is about to divide. © Dennis Kunkel Microscopy, Inc./Visuals Unlimited

Binary Fission 47 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. chromosome cell wall plasma membrane cytoplasm SEM2,345X 1. Attachment of chromosome to a special plasma membrane site indicates that this bacterium is about to divide. 2. The cell is preparing for binary fission by enlarging its cell wall, plasma membrane, and overall volume. © Dennis Kunkel Microscopy, Inc./Visuals Unlimited

Binary Fission 48 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. chromosome cell wall plasma membrane cytoplasm SEM2,345X 1. Attachment of chromosome to a special plasma membrane site indicates that this bacterium is about to divide. 2. The cell is preparing for binary fission by enlarging its cell wall, plasma membrane, and overall volume. 3. DNA replication has produced two identical chromosomes. Cell wall and plasma membrane begin to grow inward. © Dennis Kunkel Microscopy, Inc./Visuals Unlimited

Binary Fission 49 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. chromosome cell wall plasma membrane cytoplasm SEM2,345X © Dennis Kunkel Microscopy, Inc./Visuals Unlimited 1. Attachment of chromosome to a special plasma membrane site indicates that this bacterium is about to divide. 2. The cell is preparing for binary fission by enlarging its cell wall, plasma membrane, and overall volume. 3. DNA replication has produced two identical chromosomes. Cell wall and plasma membrane begin to grow inward. 4. As the cell elongates, the chromosomes are pulled apart. Cytoplasm is being distributed evenly.

Binary Fission 50 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1. Attachment of chromosome to a special plasma membrane site indicates that this bacterium is about to divide. 2. The cell is preparing for binary fission by enlarging its cell wall, plasma membrane, and overall volume. 3. DNA replication has produced two identical chromosomes. Cell wall and plasma membrane begin to grow inward. 4. As the cell elongates, the chromosomes are pulled apart. Cytoplasm is being distributed evenly. 5. New cell wall and plasma membrane has divided the daughter cells. chromosome cell wall plasma membrane cytoplasm SEM2,345X © Dennis Kunkel Microscopy, Inc./Visuals Unlimited

Functions of Cell Division 51