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The Cell Cycle Core Concepts • Cell division is necessary for reproduction, repair and growth. • The cell cycle is a continuum of processes undergone by cells during their lifetime, which involves growth and functioning, and culminates in division. • Mitosis produces two new identical cells. • Interactions of physical and chemical signals control the events of the cell cycle. • Cancer results from abnormal or lacking control signals of the cell cycle. • Meiosis is a special kind of division that produces four (4) haploid, non-identical cells. • Errors may occur during cell division, producing cells with abnormal chromosome number. Keywords • • • • • • • • • anaphase centromere chromatin chromosome crossing-over cytokinesis diploid G1 G2 • genome • haploid • homologue • interphase • kinetochore • meiosis • metaphase • mitosis • non-disjunction • prophase • sister chromatid • spindle • synthesis • telophase • tetrad The Cell Cycle Roles of Cell Division • Reproduction • Growth and development • Renewal and repair The Cell Cycle Types of cell division • Mitosis – May have evolved from binary fission in prokaryotes – Method of asexual reproduction in unicellular eukaryotes • Meiosis – Responsible for production of gametes in multicellular eukaryotes The Cell Cycle Stages of the cell cycle Important terms • genome - genetic material of a cell • chromatin – unorganized mass of DNA and proteins that condense during cell division • chromosomes – packaged DNA molecules in nuclei – somatic cells have 2 sets of chromosomes (2N, diploid) – gametes have 1 set of chromosomes (N, haploid) • interphase – preparation for cell division – – – – cell grows DNA is replicated centrosomes are replicated* chromosomes condense Eukaryotic cell division • 1 chromosome 2 sister chromatids, connected at a centromere, which separate during cell division • mitosis – division of the nucleus • cytokinesis – division of cytoplasm Mitosis consists of five distinct phases – Prophase – Prometaphase PROPHASE G2 OF INTERPHASE Centrosomes (with centriole pairs) Nucleolus Chromatin (duplicated) Nuclear envelope Plasma membrane Early mitotic spindle Aster Chromosome, consisting of two sister chromatids Centromere PROMETAPHASE Fragments of nuclear envelope Kinetochore Nonkinetochore microtubules Kinetochore microtubule – Metaphase – Anaphase – Telophase METAPHASE ANAPHASE Metaphase plate Spindle Centrosome at one spindle pole TELOPHASE AND CYTOKINESIS Cleavage furrow Daughter chromosomes Nuclear envelope forming Nucleolus forming Mitosis in a plant cell Nucleus 1 Chromatin Nucleolus condensing Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is staring to from. 2 Chromosome Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelop will fragment. 3 Metaphase. The 5 4 Telophase. Daughter Anaphase. The spindle is complete, nuclei are forming. chromatids of each and the chromosomes, Meanwhile, cytokinesis chromosome have attached to microtubules has started: The cell separated, and the at their kinetochores, plate, which will daughter chromosomes are all at the metaphase divided the cytoplasm are moving to the ends plate. in two, is growing of cell as their toward the perimeter kinetochore of the parent cell. microtubles shorten. Regulation of the Cell Cycle • Events in the cell cycle triggered and coordinated by a molecular control system • Checkpoints – critical control points where stop and go-ahead signals can regulate the cycle Restriction Point Factors that control the cell cycle 1. Telomeres – Repeated DNA sequences at tips of chromosomes – TTAGGG sequences lost every time a cell divides – Restored to their original length by telomerase (normally found in gametes) Factors that control the cell cycle 2. Regulatory proteins • Cyclins - concentration cyclically fluctuates in the cell • • Cyclin-dependent kinases (Cdks) – activate other proteins in the presence of cyclin e.g. Maturation-promoting factor (MPF) – M-phase promoted • • • – Chromatin condensation Mitotic spindle formation Degradation of nuclear envelope Deactivated when proteolytic enzymes digest the cyclin Factors that control the cell cycle 3. Growth Factors • • • proteins that stimulate other cells to divide promote the binding of cyclin to cdks ex. platelet-derived growth factor (PDGF) Factors that control the cell cycle 4. Density-dependent inhibition 5. Anchorage dependence • Most animal cells must be attached to a substrate before they can grow Cancer – uncontrolled cell division • Cells do not heed normal signals to STOP cell division • Can invade neighboring cells and interfere with normal body function • “immortal” – can keep dividing as long as nutrient supply is kept constant Transformation • Numerous diverse causes • Cancer cell tumor – Benign – Malignant • Metastasis Causes • Oncogenes – Gene that enables transformation when mutated or expressed in high levels • Viruses and bacteria – e.g. HPV and cervical cancer; Hep B and C and liver cancer; H.pylori and stomach cancer • Ionizing and UV radiation • Carcinogens Treatment • • • • Surgery Radiation Chemotherapy Immunotherapy and Gene therapy Meiosis Reductional Division for Sexual Reproduction • Types of reproduction – Asexual – Sexual • Genes – hereditary units of DNA • Locus – gene’s specific location in the chromosome Meiosis in Sexual Life Cycles • Generation-to-generation sequence of stages in the reproductive history of an organism • Homologous chromosomes – pair that has the same length, centromere position, staining pattern • Humans: 22 pairs of autosomes + 1 pair of sex chromosomes Meiosis involves 2 stages of nuclear division • Interphase – G1, S, G2 • Meiosis – Meiosis I – Meiosis II Meiosis I is reductional cell division Crossing-over during Prophase I Exchange of segments between homologous pairs • Homologues pair up tetrad • Synapsis “crossingover” that occurs at a chiasma • Does not normally happen to sex chromosomes • Purpose: to increase genetic variation Independent assortment during Metaphase I Meiosis II is equational cell division How unique are you? • Random fertilization – 1/64 million • Independent assortment – 1/223 • Crossing-over – occurs an average of 2-3 times per chromosome pair Gametogenesis 1) Meiosis - - Gametes (n) formed from embryonic primordial germ cells (PGC’s) via meiosis PGC’s (2n) meiosis sex cells (n) Spermatogonium and oogonium 2) Maturation – distinctive characteristics of sperm and egg cells are formed Spermatogenesis vs. Oogenesis SPERMATOGENESIS process is continuous 100-650 million sperm cells produced OOGENESIS unequal cytokinesis time table only 400 oocytes ovulated between puberty & menopause Spermatogenesis vs. Oogenesis 2N Suspended in prophase I One oocyte / month N N Halted at metaphase II until fertilization OOGENESIS 2 million 1o oocytes in a fetus 1 million 1o oocytes in a newborn (at prophase I) 400,000 1o oocytes during puberty (meiosis I completed in only one each month) 400 2o oocytes ovulated (at metaphase II) between puberty and menopause (meiosis II completed only after fertilization) mature ovum Questions: • How many sets of chromosomes are present in each of the following cell types? – – – – – – – an oogonium a 1o spermatocyte a spermatid a cell during anaphase I, from either sex a cell during anaphase II, from either sex a 2o oocyte a polar body derived from a 1o oocyte • Why is it extremely unlikely that a child will be genetically identical to a parent? Questions: • How do the structures of the male and female gametes aid in their functions? • A woman who is about 4 weeks pregnant suddenly begins to bleed and pass some tissue through her vagina. After a physician examines the material, he explains to her that a sperm fertilized a polar body instead of an ovum, and an embryo could not develop. What has happened? Why do you think a polar body cannot support the development of an embryo, whereas an ovum, which is genetically identical to it, can? Errors in cell division chromosomal aberrations Nondisjunction: • Pairs of homologous chromosomes do not separate normally during meiosis • Gametes contain two copies or no copies of a particular chromosome Meiosis I Nondisjunction Meiosis II Nondisjunction Gametes n+1 n+1 n 1 n–1 n+1 n –1 n Number of chromosomes (a) Nondisjunction of homologous chromosomes in meiosis I (b) Nondisjunction of sister chromatids in meiosis II n • Aneuploidy – Results from the fertilization of gametes in which nondisjunction occurred – Is a condition in which offspring have an abnormal number of a particular chromosome • If a zygote is trisomic – It has three copies of a particular chromosome • If a zygote is monosomic – It has only one copy of a particular chromosome • Klinefelter (XXY), Turner (X0) • The incidence of Down syndrome in the general population is about 1 in every 770 births. • Among women over the age of 35 years, however, the incidence of delivering a child with Down syndrome increases. • The correlation between maternal age and Down syndrome risk is striking when the age distribution for all mothers for all mothers is compares to that of mothers of Down syndrome children. • Polyploidy – Extra sets of chromosomes (3n, 4n, 5n, 6n, 8n, 10n, 12n) – Caused by nondisjunction of all chromosomes • Rare, usually fatal in animals • Common in plants (30-80%) – Polyploids often thrive better and grow taller – Solution to hybrid sterility – May be preferred because of sterility