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Cancer visualized • What is cancer? • Cancer and chemotherapy • Do naked mole rats hold the key? (click on pic to learn more) Cell Reproduction: Mitosis and Meiosis Chapters 12 and 13 Bio 1 Review Cell Reproduction Mitosis Daughter 2 cloned Only result cells are daughter in somatic 2n cells cells (diploid) Meiosis Daughter cells are n (haploid) 4 genetically shuffled daughter cells Only result in gametes LECTURE PRESENTATIONS For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson Chapter 12 The Cell Cycle Lectures by Erin Barley Kathleen Fitzpatrick © 2011 Pearson Education, Inc. What is this? Concept 12.1: Most cell division results in genetically identical daughter cells © 2011 Pearson Education, Inc. Cellular Organization of the Genetic Material • All the DNA in a cell constitutes the cell’s genome • DNA molecules in a cell are packaged into chromosomes © 2011 Pearson Education, Inc. Figure 12.3 20 m Cell Type Review • Somatic cells • Gametes – germ cells give rise to gametes © 2011 Pearson Education, Inc. Figure 12.4 In preparation for cell division, DNA is replicated and the chromosomes condense Into a chromosome, from chromatin Sister chromatids Centromere 0.5 m Figure 12.5-1 Chromosomes Mitosis overview 1 Chromosomal DNA molecules Centromere Chromosome arm Figure 12.5-2 Chromosomes Mitosis overview 1 Chromosomal DNA molecules Centromere Chromosome arm Chromosome duplication (including DNA replication) and condensation 2 Sister chromatids Figure 12.5-3 Chromosomes Replication & Mitosis 1 Chromosomal DNA molecules Centromere Chromosome arm Chromosome duplication (including DNA replication) and condensation 2 Sister chromatids Separation of sister chromatids into two chromosomes 3 Phases of the Cell Cycle • The cell cycle consists of: – Mitotic (M) phase (mitosis and cytokinesis) AND – Interphase (cell growth and copying of chromosomes in preparation for cell division) © 2011 Pearson Education, Inc. Figure 12.6 INTERPHASE G1 S (DNA synthesis) G2 Figure 12.16 G0 G1 checkpoint G1 (a) Cell receives a go-ahead signal. G1 (b) Cell does not receive a go-ahead signal. The Cell Cycle Clock: Cyclins and CyclinDependent Kinases • Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks) – Review: what do kinases do? • Example: MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G2 checkpoint into the M phase © 2011 Pearson Education, Inc. • Mitosis is conventionally divided into five phases – Prophase – Prometaphase – Metaphase – Anaphase – Telophase • Cytokinesis overlaps the latter stages of mitosis © 2011 Pearson Education, Inc. BioFlix: Mitosis © 2011 Pearson Education, Inc. 10 m Figure 12.7 G2 of Interphase Centrosomes (with centriole pairs) Nucleolus Chromatin (duplicated) Nuclear envelope Plasma membrane Prophase Early mitotic spindle Aster Centromere Chromosome, consisting of two sister chromatids Prometaphase Fragments of nuclear envelope Kinetochore Metaphase Nonkinetochore microtubules Kinetochore microtubule Anaphase Metaphase plate Spindle Centrosome at one spindle pole Telophase and Cytokinesis Cleavage furrow Daughter chromosomes Nuclear envelope forming Nucleolus forming Whitefish blastula Figure 12.8: The microtubules shorten by depolymerizing at their kinetochore ends Aster Centrosome Sister chromatids Metaphase plate (imaginary) Microtubules Chromosomes Kinetochores Centrosome 1 m Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 m The Mitotic Spindle: A Closer Look skip to diagram • The mitotic spindle is a structure made of microtubules that controls chromosome movement during mitosis • Mitosis visualization video (2 min) • In animal cells, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center © 2011 Pearson Education, Inc. • An aster (a radial array of short microtubules) extends from each centrosome – The spindle includes the centrosomes, the spindle microtubules, and the asters © 2011 Pearson Education, Inc. • During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes • Kinetochores are protein complexes associated with centromeres • At metaphase, the chromosomes are all lined up at the metaphase plate, an imaginary structure at the midway point between the spindle’s two poles © 2011 Pearson Education, Inc. 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 © 2011 Pearson Education, Inc. Animation: Cytokinesis Right-click slide / select ”Play” © 2011 Pearson Education, Inc. Animation: Animal Mitosis Right-click slide / select ”Play” © 2011 Pearson Education, Inc. Animation: Sea Urchin (Time Lapse) Right-click slide / select ”Play” © 2011 Pearson Education, Inc. Figure 12.10 (a) Cleavage of an animal cell (SEM) 100 m Cleavage furrow Contractile ring of microfilaments (b) Cell plate formation in a plant cell (TEM) Vesicles forming cell plate Wall of parent cell Cell plate 1 m New cell wall Daughter cells Daughter cells Figure 12.11 Nucleus Chromatin condensing Nucleolus 1 Prophase Chromosomes 2 Prometaphase 3 Metaphase Cell plate 4 Anaphase 10 m 5 Telophase Binary Fission in Bacteria • Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission – In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart © 2011 Pearson Education, Inc. Figure 12.12-1 Origin of replication E. coli cell 1 Chromosome replication begins. Two copies of origin Cell wall Plasma membrane Bacterial chromosome Figure 12.12-2 Origin of replication E. coli cell 1 Chromosome replication begins. 2 Replication continues. Cell wall Plasma membrane Bacterial chromosome Two copies of origin Origin Origin Figure 12.12-3 Origin of replication E. coli cell 1 Chromosome replication begins. 2 Replication continues. 3 Replication finishes. Cell wall Plasma membrane Bacterial chromosome Two copies of origin Origin Origin Figure 12.12-4 Origin of replication E. coli cell 1 Chromosome replication begins. 2 Replication continues. 3 Replication finishes. 4 Two daughter cells result. Cell wall Plasma membrane Bacterial chromosome Two copies of origin Origin Origin 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 © 2011 Pearson Education, Inc. Figure 12.18: Figure 12.18 The effect of platelet-derived growth factor (PDGF) on cell division. 1 A sample of human connective tissue is cut up into small pieces. Scalpels Petri dish 2 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. 3 Cells are transferred to culture vessels. Without PDGF 4 PDGF is added to half the vessels. With PDGF 10 m External signals associated with cell cycle • A clear example of external signals is densitydependent 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 ****Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence © 2011 Pearson Education, Inc. Figure 12.19 Anchorage dependence Density-dependent inhibition Density-dependent inhibition 20 m 20 m (a) Normal mammalian cells (b) Cancer cells Loss of Cell Cycle Controls in Cancer Cells • Cancer cells do not respond normally to the body’s control mechanisms • Why cancer cells make tumors: – They may make their own growth factor – They may convey a growth factor’s signal without the presence of the growth factor – They may have an abnormal cell cycle control system © 2011 Pearson Education, Inc. Growth Factors and Cancer • Growth factors can create cancers – proto-oncogenes • normally activates cell division – growth factor genes – become oncogenes (cancer-causing) when mutated • if switched “ON” can cause cancer • example: RAS (activates cyclins) – tumor-suppressor genes • normally inhibits cell division • if switched “OFF” can cause cancer • example: p53 Cancer & Cell Growth • Cancer is essentially a failure of cell division control – unrestrained, uncontrolled cell growth • What control is lost? – lose checkpoint stops – gene p53 plays a key role in G1/S restriction point p53 is the Cell Cycle Enforcer • p53 protein halts cell division if it detects damaged DNA – options: » stimulates repair enzymes to fix DNA » forces cell into G0 resting stage » keeps cell in G1 arrest » causes apoptosis of damaged cell • ALL cancers have to shut down p53 activity p53 discovered at Stony Brook by Dr. Arnold Levine p53 — master regulator gene NORMAL p53 p53 allows cells with repaired DNA to divide. p53 protein DNA repair enzyme p53 protein Step 1 Step 2 Step 3 DNA damage is caused by heat, radiation, or chemicals. Cell division stops, and p53 triggers enzymes to repair damaged region. p53 triggers the destruction of cells damaged beyond repair. ABNORMAL p53 abnormal p53 protein Step 1 Step 2 DNA damage is caused by heat, radiation, or chemicals. The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA. cancer cell Step 3 Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous. Key mutations causing Cancer • Cancer develops only after a cell experiences ~6 key mutations (“hits”) 1. unlimited growth turn on growth promoter genes 2. ignore checkpoints turn off tumor suppressor genes (p53) 3. escape apoptosis turn off suicide genes 4. immortality = unlimited divisions turn on chromosome maintenance genes 5. promotes blood vessel growth turn on blood vessel growth genes 6. overcome anchor & density dependence turn off touch-sensor gene What causes these “hits”? • Mutations in cells can be triggered by UV radiation chemical exposure radiation exposure heat cigarette smoke pollution age genetics Tumors • Mass of abnormal cells – Benign tumor • abnormal cells remain at original site as a lump – p53 has halted cell divisions • most do not cause serious problems & can be removed by surgery – Malignant tumor • cells leave original site – lose attachment to nearby cells – carried by blood & lymph system to other tissues – start more tumors = metastasis • impair functions of organs throughout body Traditional treatments for cancers • Treatments target rapidly dividing cells – high-energy radiation • kills rapidly dividing cells – chemotherapy • stop DNA replication • stop mitosis & cytokinesis • stop blood vessel growth New “miracle drugs” • Drugs targeting proteins (enzymes) found only in cancer cells – Gleevec • treatment for adult leukemia (CML) & stomach cancer (GIST) • 1st successful drug targeting only cancer cells without Gleevec Novartes with Gleevec Figure 12.21 Figure 12.UN02 REVIEW: Can you identify the phases of the cell cycle? Figure 12.UN05 Figure 12.UN05 Figure 12.UN04 Why do humans have a sex drive? MEIOSIS BIG THEME: • Meiosis is the key to genetic diversity of offspring, thus the key to evolution, and by extension, the key to sex drive LECTURE PRESENTATIONS For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson Chapter 13 Meiosis and Sexual Life Cycles Lectures by Erin Barley Kathleen Fitzpatrick © 2011 Pearson Education, Inc. Figure 13.1: What accounts for family resemblance? Mitosis vs. Meiosis animation - NOVA • The difference is really simple. Just one step. Concept 13.1: Offspring acquire genes from parents by inheriting chromosomes • See the title © 2011 Pearson Education, Inc. Inheritance of Genes: review • Terms: Gametes, genes, locus, (pl. loci) © 2011 Pearson Education, Inc. Asexual vs. Sexual Reproduction • Asexual reproduction • sexual reproduction © 2011 Pearson Education, Inc. Video: Hydra Budding © 2011 Pearson Education, Inc. Reproduction without sex can work 0.5 mm Parent Bud Concept 13.2: Fertilization and meiosis alternate in sexual life cycles © 2011 Pearson Education, Inc. Lets review chromosome basics Lets review chromosome basics terms: somatic cells, homologues (or homologous pairs), diploid (vs. haploid), 2n, n, sex chromosomes, autosomes Figure 13.3 APPLICATION A karyotype is an ordered display of the pairs of chromosomes from a cell TECHNIQUE Pair of homologous duplicated chromosomes Centromere Sister chromatids Metaphase chromosome 5 m Describing chromosomes Key 2n 6 Maternal set of chromosomes (n 3) Paternal set of chromosomes (n 3) Sister chromatids of one duplicated chromosome Two nonsister chromatids in a homologous pair Centromere Pair of homologous chromosomes (one from each set) • A gamete (sperm or egg) contains a single set of chromosomes, and is haploid (n) • For humans, the haploid number is 23 (n = 23) – Each set of 23 consists of 22 autosomes and a single sex chromosome – In an unfertilized egg (ovum), the sex chromosome is X – In a sperm cell, the sex chromosome may be either X or Y © 2011 Pearson Education, Inc. Behavior of Chromosome Sets in the Human Life Cycle • Fertilization is the union of gametes (the sperm and the egg) – The fertilized egg is called a zygote and has one set of chromosomes from each parent – The zygote produces somatic cells by mitosis and develops into an adult © 2011 Pearson Education, Inc. Figure 13.5 Haploid gametes (n 23) Key Haploid (n) Diploid (2n) Egg (n) Sperm (n) MEIOSIS Ovary FERTILIZATION Testis Diploid zygote (2n 46) Mitosis and development Multicellular diploid adults (2n 46) Can you find difference? 3 types of organismal life cycles Key Haploid (n) Diploid (2n) n Gametes n Mitosis n n MEIOSIS FERTILIZATION n Diploid multicellular organism (a) Animals Zygote 2n Mitosis n Mitosis n Mitosis n Spores Gametes MEIOSIS 2n Haploid unicellular or multicellular organism Haploid multicellular organism (gametophyte) n n n n Gametes FERTILIZATION 2n Zygote Mitosis (b) Plants and some algae n FERTILIZATION MEIOSIS 2n Diploid multicellular organism (sporophyte) Mitosis 2n Zygote (c) Most fungi and some protists Figure 13.6 3 types of organismal life cycles Key Haploid (n) Diploid (2n) n Gametes n Mitosis n n MEIOSIS FERTILIZATION n Diploid multicellular organism (a) Animals Zygote 2n Mitosis n Mitosis n Mitosis n Spores Gametes MEIOSIS 2n Haploid unicellular or multicellular organism Haploid multicellular organism (gametophyte) n n n n Gametes FERTILIZATION 2n Zygote Mitosis (b) Plants and some algae n FERTILIZATION MEIOSIS 2n Diploid multicellular organism (sporophyte) Mitosis 2n Zygote (c) Most fungi and some protists Plants and some algae exhibit an alternation of generations • This life cycle includes both a diploid and haploid multicellular stage • The diploid organism, called the sporophyte, makes haploid spores by meiosis Concept 13.3: Meiosis reduces the number of chromosome sets from diploid to haploid • What does this mean? © 2011 Pearson Education, Inc. Meiosis overview Interphase Pair of homologous chromosomes in diploid parent cell Duplicated pair of homologous chromosomes Sister chromatids Chromosomes duplicate Diploid cell with duplicated chromosomes Figure 13.7-2 Interphase Pair of homologous chromosomes in diploid parent cell Duplicated pair of homologous chromosomes Sister chromatids Chromosomes duplicate Diploid cell with duplicated chromosomes Meiosis I 1 Homologous chromosomes separate Haploid cells with duplicated chromosomes Figure 13.7-3 Interphase Pair of homologous chromosomes in diploid parent cell Duplicated pair of homologous chromosomes Sister chromatids Chromosomes duplicate Diploid cell with duplicated chromosomes Meiosis I 1 Homologous chromosomes separate Haploid cells with duplicated chromosomes Meiosis II 2 Sister chromatids separate Haploid cells with unduplicated chromosomes BioFlix: Meiosis © 2011 Pearson Education, Inc. Meiosis: Step by step Figure 13.8 MEIOSIS I: Separates sister chromatids MEIOSIS I: Separates homologous chromosomes Prophase I Metaphase I Centrosome (with centriole pair) Sister chromatids Chiasmata Telophase I and Cytokinesis Anaphase I Duplicated homologous chromosomes (red and blue) pair and exchange segments; 2n 6 in this example. Anaphase II Telophase II and Cytokinesis Centromere (with kinetochore) Metaphase plate Cleavage furrow Fragments of nuclear envelope Metaphase II Sister chromatids remain attached Spindle Homologous chromosomes Prophase II Homologous chromosomes separate Microtubule attached to kinetochore Chromosomes line up by homologous pairs. Each pair of homologous chromosomes separates. During another round of cell division, the sister chromatids finally separate; four haploid daughter cells result, containing unduplicated chromosomes. Sister chromatids separate Two haploid cells form; each chromosome still consists of two sister chromatids. Haploid daughter cells forming Figure 13.8a Prophase I Centrosome (with centriole pair) Sister chromatids Chiasmata Spindle Telophase I and Cytokinesis Anaphase I Metaphase I Sister chromatids remain attached Centromere (with kinetochore) Metaphase plate Fragments Homologous chromosomes of nuclear envelope Homologous chromosomes separate Microtubule attached to kinetochore Cleavage furrow Each pair of homologous chromosomes separates. Chromosomes line up Duplicated homologous chromosomes (red and blue) by homologous pairs. pair and exchange segments; 2n 6 in this example. Two haploid cells form; each chromosome still consists of two sister chromatids. Prophase I –where meiosis differs from mitosis • Prophase I typically occupies more than 90% of the time required for meiosis, chromosomes begin to condense • In synapsis, homologous chromosomes loosely pair up, aligned gene by gene, forming a tetrad © 2011 Pearson Education, Inc. • In crossing over, nonsister chromatids exchange DNA segments – Each pair of chromosomes forms a tetrad, a group of four chromatids • Each tetrad usually has one or more chiasmata, X-shaped regions where crossing over occurred © 2011 Pearson Education, Inc. Figure 13.8b Prophase II Metaphase II Anaphase II Telophase II and Cytokinesis During another round of cell division, the sister chromatids finally separate; four haploid daughter cells result, containing unduplicated chromosomes. Sister chromatids separate Haploid daughter cells forming Figure 13.9a MEIOSIS MITOSIS Parent cell MEIOSIS I Chiasma Prophase I Prophase Duplicated chromosome Chromosome duplication 2n 6 Chromosome duplication Homologous chromosome pair Metaphase Metaphase I Anaphase Telophase Anaphase I Telophase I Daughter cells of meiosis I 2n Daughter cells of mitosis 2n Haploid n3 MEIOSIS II n n n n Daughter cells of meiosis II Figure 13.9b SUMMARY Property Mitosis Meiosis DNA replication Occurs during interphase before mitosis begins Occurs during interphase before meiosis I begins Number of divisions One, including prophase, metaphase, anaphase, and telophase Two, each including prophase, metaphase, anaphase, and telophase Synapsis of homologous chromosomes Does not occur Occurs during prophase I along with crossing over between nonsister chromatids; resulting chiasmata hold pairs together due to sister chromatid cohesion Number of daughter cells and genetic composition Two, each diploid (2n) and genetically identical to the parent cell Four, each haploid (n), containing half as many chromosomes as the parent cell; genetically different from the parent cell and from each other Role in the animal body Enables multicellular adult to arise from zygote; produces cells for growth, repair, and, in some species, asexual reproduction Produces gametes; reduces number of chromosomes by half and introduces genetic variability among the gametes comparison MITOSIS MEIOSIS Parent cell MEIOSIS I Chiasma Prophase I Prophase Duplicated chromosome Chromosome duplication 2n 6 Chromosome duplication Homologous chromosome pair Metaphase Metaphase I Anaphase Telophase Anaphase I Telophase I Daughter cells of meiosis I 2n Haploid n3 MEIOSIS II 2n Daughter cells of mitosis n n n n Daughter cells of meiosis II SUMMARY Property Mitosis Meiosis DNA replication Occurs during interphase before mitosis begins Occurs during interphase before meiosis I begins Number of divisions One, including prophase, metaphase, anaphase, and telophase Two, each including prophase, metaphase, anaphase, and telophase Synapsis of Does not occur homologous chromosomes Occurs during prophase I along with crossing over between nonsister chromatids; resulting chiasmata hold pairs together due to sister chromatid cohesion Two, each diploid (2n) and genetically Number of daughter cells identical to the parent cell and genetic composition Four, each haploid (n), containing half as many chromosomes as the parent cell; genetically different from the parent cell and from each other Role in the animal body Enables multicellular adult to arise from zygote; produces cells for growth, repair, and, in some species, asexual reproduction Produces gametes; reduces number of chromosomes by half and introduces genetic variability among the gametes Concept 13.4: Genetic variation produced in sexual life cycles contributes to evolution • Three mechanisms contribute to genetic variation from sexual reproduction: • Shuffling of alleles: 1. Independent assortment of chromosomes 2. Crossing over • Mating process 3. Random fertilization of sperm 4. Also, mutations occur in all organisms © 2011 Pearson Education, Inc. Math test: • How many chromosome combinations are possible in a given human gamete, not including crossing over or mutations? Statistics of meiotically-derived diversity • The number of combinations possible when chromosomes assort independently into gametes is 2n, where n is the haploid number – For humans (n = 23), there are more than 8 million (223) possible combinations of chromosomes © 2011 Pearson Education, Inc. Independent assortment visualized Possibility 2 Possibility 1 Two equally probable arrangements of chromosomes at metaphase I Independent assortment visualized Possibility 2 Possibility 1 Two equally probable arrangements of chromosomes at metaphase I Metaphase II Independent assortment visualized Possibility 2 Possibility 1 Two equally probable arrangements of chromosomes at metaphase I Metaphase II Daughter cells Combination 1 Combination 2 Combination 3 Combination 4 Crossing Over • Crossing over produces recombinant chromosomes, which combine DNA inherited from each parent into a single cromosome – Crossing over begins very early in prophase I, as homologous chromosomes pair up gene by gene – homologous portions of two nonsister chromatids trade places © 2011 Pearson Education, Inc. • In crossing over, homologous portions of two nonsister chromatids trade places • Crossing over contributes to genetic variation by combining DNA from two parents into a single chromosome © 2011 Pearson Education, Inc. Figure 13.11-1 Prophase I of meiosis Pair of homologs Nonsister chromatids held together during synapsis Figure 13.11-2 Prophase I of meiosis Pair of homologs Chiasma Centromere TEM Nonsister chromatids held together during synapsis Figure 13.11-3 Prophase I of meiosis Pair of homologs Chiasma Centromere TEM Anaphase I Nonsister chromatids held together during synapsis Figure 13.11-4 Prophase I of meiosis Pair of homologs Chiasma Centromere TEM Anaphase I Anaphase II Nonsister chromatids held together during synapsis Figure 13.11-5 Prophase I of meiosis Nonsister chromatids held together during synapsis Pair of homologs Chiasma Centromere TEM Anaphase I Anaphase II Daughter cells Recombinant chromosomes Random Fertilization and variation • Random fertilization adds to genetic variation because any sperm can fuse with any ovum (unfertilized egg) • Fun Tidbit: The fusion of two gametes (each with 8.4 million possible chromosome combinations from independent assortment) produces a zygote with any of about 70 trillion diploid combinations – Crossing over and mutations add even more variation © 2011 Pearson Education, Inc. Animation: Genetic Variation Right-click slide / select “Play” © 2011 Pearson Education, Inc. Figure 13.12 A bdelloid rotifer, an animal that reproduces only asexually How do they survive evolutionarily? 200 m