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1 Chapter 12 How cells divide Reproduction living /non-living? growth repair renew based on cell division first mitosis - distributes identical sets of chromosomes cell cycle (life) Cell Division in Bacteria and Eukaryotic Cells Eukaryotic Chromosomes Phases of the Cell Cycle, including Interphase Chromosomes during Mitosis Cytokinesis Cell Cycle Control Cancer Reproduction living /non-living based on cell division First mitosis (thread, 1882) distributes identical sets of chromosomes fertilized egg (zygote) next chapter 1

2 identical sets of chromosomes genetic material (genome) DNA to two daughter cells A dividing cell 1) duplicates DNA (3 meters!) 2) copies to opposite ends 3) splits Prokaryotic binary fission a single, circular double-stranded DNA molecule - replicates, one genome to each daughter cell prokaryotes -single DNA molecule eukaryotes more complex packaged into chromosomes characteristic number Human somatic cells (body cells) - 46 Extra # 21? Next chapter human gamete (wife) sperm or egg 23 - half (haploid) 2

3 Males X Y Females XX note Y is small Lots of CNS genes on X autosomes - rest kayrotype Humans (Most Animals) Diploid Number of different chromosomes = n Diploid cells have two copies (2n) of each chromosome (homologues) Humans 2n = 46 poly, triploid some oysters, lizards, catfish Homologues -not identical variants Each chromosome hundreds or thousands of genes wrapped around proteins - maintain structure DNA complex: nucleotides, histone proteins (nucleosome) chromatin - long thin fiber Following duplication, chromatin condenses narrow area - centromere 3

4 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Scaffold protein Scaffold protein Solenoid Chromosome Rosettes of chromatin loops 30 nm DNA Central histone Chromatin loop Nucleosome DNA DNA double helix (duplex) DNA replication... has this effect at chromosomal level unduplicated chromosome (not actual shape) duplicated chromosome sister chromatids Homologous chromosomes are made up of sister chromatids joined at the centromere (still one) Sister replications Homologous same chromosome Karyotype - homologous 4

5 Cell Descendants Have All DNA Information Duplication of both cytoplasmic and nuclear contents precedes division cell nucleus DNA DNA DNA DNA 1. REPLICATION 2. MITOSIS (division of nucleus) DNA 3. CYTOKINESIS (division of cytoplasm) DNA DNA Phases of the Cell Cycle Five phases of cell division: G 1 - primary growth phase (gap 1) S - genome replicated (synthesis) G 2 - secondary growth phase (prepare to separate) Together called interphase M - mitosis C - cytokinesis Cell Cycle (mitosis small portion) 5

6 repeating pattern of growth, duplication, and division Mammals 24 hours (Embryos 20 min) (some liver cells 1 yr) Two main phases interphase mitotic phase (about minutes) Most variability here PAUSE G 0 resting (not really) Interphase (approximately 90%) 3 stages lead up to division: G 1 (gap 1 for growth 12 hours) normal growth S phase (synthesis, for replication of DNA 6 hours) G 2 (gap 2 6 hours) cytoplasm growth Cell Division: M Phase Mitosis duplicated chromosomes (sister chromatids -still attached) condense, align themselves, and separate four stages Prophase Metaphase Anaphase Telophase Cytokinesis Cell s cytoplasm and membrane separate to create two distinct cells PMATC!! 6

7 PMATC Politics Makes Anyone Terribly Corrupt People Might Assassinate The Cat Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chromatid Kinetochore microtubules Kinetochore Centromere region of chromosome Metaphase chromosome Mitosis: Prophase Chromosomes condense nuclear envelope breaks down spindle fibers (microtubules) are formed from the centrosome region (location of Centroles) 7

8 Mitotic Spindle made of microtubules microtubules are composed of protein called tubulin tubulin units can assemble and disassemble to rearrange microtubules (lego) Mitosis:Metaphase Chromosomes aligned at equator each sister chromatid facing opposite pole Mitosis: Anaphase Sister chromatids separate each new chromosome moves to the opposite pole. 8

9 Mitosis: Telophase Chromosomes decondense spindle breaks down nuclear envelope forms Cytokinesis (begins back in anaphase) contractile ring (protein filaments) forms cleavage furrow pinches cells apart Membrane fusion Plants are different in telophase, vesicles (from Golgi) coalesce at metaphase plate Cell plate enlarges until membranes fuse with plasma membrane Fig

10 Plant cells have cell wall OUTSIDE membrane Vesicles (filled w/sugar) fuse near the metaphase plate CYTOKINESIS IN PLANTS cell wall vesicles plasma membrane cell plate two daughte r cells Membrane-lined vesicles accumulate near the metaphase plate. The vesicles contain precursors to the cell wall. Vesicles fuse together, forming a cell plate that grows toward the parent cell wall. The newly formed plasma membrane and cell wall fuse with the parent plasma membrane and cell wall, forming two distinct daughter cells. form a cell plate that grows outward to form a cell wall jump from binary fission to mitosis? intermediate evolutionary steps? Cell Cycle 10

11 timing and rates differ skin cells liver cells nerve cells muscle cells chemical signals molecules trigger and coordinate key events in the cell cycle checkpoints checkpoint - critical control points stop and go signals regulate cycle cellular surveillance mechanisms signals outside cell 3 major checkpoints G 1 /S G 2 /M Spindle Cell Control Cycle G 1 / S - primary division decision point - external signals important, DNA also G 2 / M - commitment to mitosis - Cdk s, DNA Spindle checkpoint - chromosomes are attached to spindle 11

12 activity of control molecules pace cell cycle protein kinases (enzymes) activate or deactivate other proteins by phosphorylating them kinases require a second protein (cyclin) to become activated cyclin-dependent kinases (Cdks) Levels fluctuate Cyclin levels rise in interphase, fall abruptly during mitosis Cdk and Cyclin complex triggers passage through checkpoints following phosphorlation G 1 /S- important If no go-ahead signal, cell exits cycle -nondividing G 0 phase Most human cells in G 0 phase some called back by external cues (growth factors) 12

13 G 1 checkpoint regulated by Cdk proteins and cyclins still under investigation! MPF ( maturationpromoting factor or M-phase-promotingfactor ) triggers passage past G 2 checkpoint promotes mitosis by phosphorylating other protein kinases. triggers breakdown of cyclin cyclin and MPF levels drop during mitosis MPF inactivated Spindle checkpoint - all chromosomes attached to spindle at metaphase plate before anaphase ensures that daughter cells do not end up with missing or extra chromosomes checkpoints can fail 13

14 Growth Factors and the Cell Cycle growing cells bind growth factors (over 50 kinds) trigger intercellular signaling systems What happens if there is not enough? Cancer and Cell Proliferation Cancer - failure of cell division control gene p53 plays a role in G 1 checkpoint halts cell division if detects damaged DNA and stimulates activity of repair enzymes absent or damaged in many cancerous cells (50% of human cancers!) (cigarettes mutate it) growth factors- stimulate other cells to divide platelet-derived growth factors (PDGF) produced by platelet blood cells bind to tyrosine-kinase receptors of fibroblasts (connective tissue) triggers signal-transduction pathway that leads to cell division 14

15 role of PDGF - cell culture Fibroblasts only divide in medium that contains PDGF Why do we care?? Near injury platelets release PDGF proliferation of fibroblasts help heal the wound but can proliferate uncontrollably if checkpoints fail Growth Factors and Cancer Growth factors influence cell cycle proto-oncogenes - normal cellular genes that become oncogenes when mutated positive approach that stimulates cell growth tumor-suppressor genes - negative approach that inhibits cell division 15

16 CANCER density-dependent inhibition Growth factors - key in density-dependent inhibition Cultured cells form a single layer and stop If gap created, cells grow to fill gap anchorage dependence cells anchored typically to extracellular matrix of tissue. plasma membrane proteins and cytoskeletal elements Cancer cells - no density-dependent inhibition or anchorage dependence. Cancer cells lose cell cycle controls do not stop dividing manufacture own growth factor abnormality in the signaling pathway problem in the cell cycle control system stop at random points not checkpoints 16

17 mammalian cells in culture -divide 20 to 50 times -stop, age, die cancer cells may be immortal?! HeLa cells (HeLa) (tumor Henrietta Lacks) reproducing since 1951 transformation converts from normal cell to cancer cell mitotic count - grade 1-3 immune system recognizes destroys transformed cells Not all - tumor, mass of abnormal cells. If remain at originating site - benign tumor If leave site to impair one or more organsmalignant metastasis lose attachment carried by the blood and lymph system start more tumors 17

18 how do cells die? apoptosis -programmed? cell death webbed fingers brain cells different (neurogenesis) high-energy radiation and chemotherapy selectively target actively dividing cells Cancer - diverse reasons always involves alteration of genes that influence cell cycle control system. 18

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