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University of Pittsburgh
Biological Sciences
BIOSC 0160

Mitotic Cell Cycle Chapter 11 MITOTIC CELL CYCLE I. Cell Division a. Functions i. Reproduction 1. E.g. unicellular forms 2. E.g. in asexual multicellular form ii. Development 1. Cell division of zygote iii. Growth 1. Cellular division increases sizes of structure iv. Tissue Maintenance and Repair 1. Wound healing b. Distribution of materials between daughter cells i. Genome copied, distributed to daughter cells ii. Cytoplasm partitioned including: mitochondria, ribosomes, plastids, localized RNA c. Eukaryotes vs. Prokaryotes i. Eukaryotes: Mitosis (nuclear division) and Cytokinesis (splitting of cytoplasm) ii. Prokaryotes: Binary Fission (no nucleus to divide) d. Diversity in modes of cell division i. There is GREAT diversity in modes ii. Focus on typical Eukaryotic mode II. Chromosomes and Chromatin a. Eukaryotic chromosome i. Linear ii. Consist of complex of DNA and protein (chromatin) iii. Chromosome bears genes 1. Genes are present in “euchromatin” (true chromatin; undergoes condensation and relaxation) iv. Chromosome also bears non-DNA (heterochromatin) v. Chromosome number varies between species 1. Humans 46 2. Mouse 40 3. Drosophila 8 4. Adder’s tongue fern 1262 b. Chromatin (Fig 18.2 pg. 321) i. Material making up chromosome ii. DNA protein complex making up eukaryotic chromosome iii. Functions: 1. DNA packing and chromosome condensation 2. Regulation of gene expression c. Packing of Chromatin i. Can be fully extended, fully condensed, or somewhere in between ii. There is a hierarchy at packing iii. Most basic level 1. DNA wrapped around a nucleosome (“bead”) –most relaxed stage 2. Each nucleosome consist of four histones: H2A, H2B, H3, H4 Mitotic Cell Cycle Chapter 11 3. 2 of each histone type (8 all together) 4. H1 protein is not part of nucleosome; but attaches nucleosome to DNA iv. Next level 1. H1 histone binds to nucleosome, can cause 30-nm chromatin fiber to form a. Caused by interaction of other H1 histones together; wraps up all DNA, NO linker DNA 2. Gene expression turned on and off by relaxation of condensing into 30-nm chromatin fiber v. Next level 1. Fully condensed chromosome 2. Chromatin at least extended state 3. Protein scaffold folds on itself somehow to be fully condensed vi. Overall 1. An elegant adaptation to packing problem 2. Shows hierarchy organization 3. Sets up well for gene regulation d. Karyotypes (fig 12.1 pg 212, 15.9) i. Karyotype: the array of chromosomes an individuals cells bear ii. Also a picture of the array iii. Karyotypes are prepared when cells are in metaphase of mitosis iv. This is when chromosomes are fully condensed III. The Eukaryotic Cell Cycle a. Overview: G1-S-G2-M(m and c) i. Cells go through events and phases ii. Together these make up cell cycle iii. Interphase  grow; copy chromosomes 1. G1-S-G2 iv. M Phase – mitosis and cytokinesis b. G1 events i. “Gap 1” ii. Growth iii. Production of cytoplasm organelles iv. Preparation for chromosome duplication v. Longest part of interphase c. S Phase i. “Synthesis” ii. DNA replication iii. Chromosome duplication iv. Centrosome replication (microtubules organizing center) v. Continued growth d. G2 events i. “Gap 2” ii. Continued growth iii. Preparation for mitosis 1. Two centrosomes present; each with a pair of centrioles e. Mitosis i. Prophase 1. Start of mitotic spindle (spindle apparatus) formation (made of microtubules) Mitotic Cell Cycle Chapter 11 2. Start chromosome condensation ii. Prometaphase 1. Nuclear envelope fragments 2. Kinetochore forms at centromere (place where duplicated chromosomes held together) 3. Microtubules attach to kinetochores 4. Polar microtubules do not attach to kinetochores iii. Metaphase 1. Condensed chromosomes line up at “metaphase plate” 2. Each chromosome consist of two sister chromatids iv. Anaphase 1. Each centromere splits (centromere # = chromosome #) 2. Sister chromatids move to opposite poles 3. Once sister chromatids separate, they each become a chromosome 4. Kinetochore microtubules (motor protein) shorten, causing this movement 5. Polar microtubules extend through metaphase plate and align with one another and slide by each other elongating the cell (fig 11.8 pg 201) 6. Shortening of microtubules occurs at kinetochore 7. Implicates motor protein at kinetochore v. Telophase 1. Daughter nuclei form 2. Chromosomes “de-condense” f. Cytokinesis i. Begins in telophase ii. Cleavage furrow (animals) or cell plate (plants) forms 1. Actin and myosin filaments slide by one another making cleavage furrow 2. Plants have vesicles that bring cellulose to make cell plate iii. Two separate cells are the result g. Binary Fission i. Bacteria DO NOT undergo Mitosis** ii. Circular bacterial chromosome replicates 1. Circular and much smaller than Eukaryotes 2. Do Not have histones iii. Each copy attaches to plasma membrane at adjacent sites iv. Septum forms in middle of cell 1. Involves protein like FtsZ (splits cells) a. Filaments temperature sensitive b. Similar to tubulin protein c. Mitosis evolves from Binary Fission (fig 11.7 pg 200) IV. Regulation of the cell cycle a. Cell cycle control system and cell cycle checkpoints i. Cell cycle is normally tightly controlled ii. Checkpoints 1. Stop signals 2. Overridden by “go-ahead” signals 3. Cell has surveillance mechanisms to make sure things are okay iii. G1 checkpoint (restriction point) 1. Cells that stop here enter Go Mitotic Cell Cycle Chapter 11 2. If passes G1 it must finish cycle…or die iv. Two other: G2-M and Metaphase checkpoint 1. G2 If DNA damaged, gene P53 tries to fix or dies (apoptosis) 2. M  chromosomes align and all kinetochores properly attached b. Cyclin and Cyclin-dependent kinase i. Kinases: enzymes that add phosphate groups to substrates ii. Cdk’s present all the time but not always active iii. Cdk’s activated by cyclins 1. Cyclins are proteins 2. Build up during G1, S, and G2 3. Each checkpoint has its own cyclin 4. An example a. Consider cyclin specific to G2/M checkpoint (M-phase specific cyclin B) binds to and activates MPF (Maturation Promoting Factor/Cdk1) b. Cdk1-cylcin B complex is an activated kinase c. Pushes cell past G2/M checkpoint d. Causes nuclear envelope to fragment e. Activates other kinases at G2 checkpoint 5. Also Cdk must be properly phosphorylated to be active 6. Details of signaling not completely known c. Internal and External Cues i. Internal: Cdk1-cyclinB complex ii. External: growth factors (growth hormones) V. Cancer  when cells escape cell-cycle control a. Transformation - converts normal cell into cancer cell b. Benign Tumor – abnormal cells remain at original site c. Malignant Tumor – abnormal cells are invasive (spread) d. Metastasis – spread of malignant cells e. Cells can divide indefinitely f. i.e. they never die or enter G o g. e.g. Hela cells Mitotic Cell Cycle Chapter 11 MEIOSIS I. Modes of Reproduction a. Asexual i. One parent only ii. Parent passes all genes to offspring iii. Offspring virtually identical to parent b. Sexual i. Two parents ii. Each passes ½ of genes to offspring iii. Offspring differ from parents and each other c. Parthenogentic i. Egg develops without being fertilized ii. May occur with or without meiosis II. Concept of a life cycle a. Definition of “life cycle” i. Sequence of stages and events in the reproductive history of an organism ii. From fertilization to reproduction b. Terms that deal with chromosomes i. Homologous (basic) chromosome 1. Homologs if same: length, centromere position, gene order ii. Karyotype 1. Complete set of chromosomes of an organism or cell 2. Photograph display of this set iii. Autosomes 1. Non-sex chromosomes iv. Sex chromosomes 1. Non-homologous: X and Y (humans) 2. Birds: ZZ-male ….ZW-female c. Terms with concept of ploidy i. Ploidy 1. Number of each different type of basic chromosome in an organism or cell ii. Haploid n 1. Possession of only 1 of each chromosome iii. Diploid2n 1. Possession of 2 of each basic chromosome III. Meiosis (gamete formation) a. Reduction in chromosomes number from diploid to haploid i. Haploid cells have 1 of each chromosome ii. Haploid gametes will join at fertilization to make diploid again b. Meiosis 1 – separate homologous chromosomes i. Interphase 1 1. Chromosomes replicate 2. Centrosome replicates ii. Prophase 1 1. Nuclear envelope fragments 2. Chromosomes condense Mitotic Cell Cycle Chapter 11 3. Homologous chromosomes synapse (Table 12.2 pg 214) a. Yields tetrads consisting of 4 chromatids 4. Crossing-over occurs a. Crossing-over called chiasmata b. Homologous exchange segments (non-sister chromatids) 5. Spindle apparatus forms 6. Prophase 1 is a long process iii. Metaphase 1 1. Tetrads align at metaphase plate iv. Anaphase 1 1. Homologous chromosomes separate v. Telophase 1 and Cytokinesis 1 1. Homologs reach poles 2. Cleavage furrow forms (animals) 3. Each cell has haploid set, each chromosome consisting of two chromatids c. Meiosis II (separates sister chromatids) i. Similar to mitosis (very similar) ii. Important distinctions 1. NO DNA replication occurs before meiosis II 2. Starting cells are haploid 3. Product of meiosis II: gametes IV. Meiosis and the origin of gamete variation a. Ultimate source of gamete variation: mutation b. Recombination generates gamete variation i. Crossing-over yields novel gene combination c. Alternate alignment at metaphase 1 increases variation i. Different chromosomes assort independently during anaphase 1 ii. Each tetrad can align in two different ways (8 million possibilities) Mitotic Cell Cycle Chapter 11 MENDEL’S LAWS I. Heredity a. Concept i. Offspring resemble parents ii. Offspring virtually identical to parents in asexual forms iii. Offspring similar to parents in sexual forms iv. Basis: Inherited genetic information b. State of understating in 1850 i. Merely that offspring resemble parents ii. Mechanism simply was not known iii. A BIG pr
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