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Lecture 7

Lecture 7 - Mitosis & Cell Cycle Control.docx

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Biology 2382B
Jessica Kelly

Lecture 7/8 - Mitosis & Cell Cycle Control (Chp 18: p. 781-783) (Chp 20: p. 847-853, p. 858-863, p. 887) Function of the Cell Cycle • Essential mechanism by which all living things reproduce and pass on genetic information to next generation of cells • Ensures that DNA in each chromosome is faithfully replicated to produce 2 copies • Replicated chromosomes must be accurately distributed (segregated) to 2 genetically identical daughter cells • Coordination of growth (increase in cell mass) with division Checkpoints exist during the cycle to ensure that each daughter cell has the same full set of chromosomes segregated properly and has grown sufficiently that the daughter cells will be viable upon division…research has shown these mechanisms are highly conserved among all eukaryotic cells… The Cell Cycle & Its Phases Cell cycle - the ordered sequence of events in which a cell duplicates its chromosomes and divides into two genetically identical cells 4 Phases: G1-S-G2 = Interphase  Cell increases in size • In M phase (mitosis) most dramatic events can be observed microscopically All Cells are generated from pre-existing cells…  Difficult to determine where a cell is in interphase but easy when in Mitosis… 1 Phases of The Cell Cycle FACS  can be used to quantify proportion of cells are in each cell cycle phase  This is achieved by measuring the intensity of fluorescence from the Hoescht stain bound to DNA  at the end of S phase cell has double the DNA and therefore fluorescence intensity is also doubled… G1 being the longer phase of the cell cycle means that more cells are likely to be in this phase of the cell cycle… G 1Gap 1) Phase:  Generalized growth and metabolism of the cell  Where most cells arrest when not dividing (i.e. enter G ) o  Variable length (~11 hours in mammalian cells) S (Synthesis) Phase:  DNA replication occurs (~6-8 hours)  Cell stops actively metabolizing during this pahase G2 (Gap 2) Phase:  Preparation for chromosome segregation and cell division (~4 hours) M (Mitosis) Phase:  Chromatin condensation  Nuclear envelope breakdown (retracts into ER)  Sister chromatids attach to mitotic spindle (which duplicates)  Segregation of chromatids  Decondense and reformation of intact nuclei  Cytokinesis (~1 hour) G1 being the longer phase of the cell cycle means that more cells are likely to be in this phase of the cell cycle… Some Eukaryotic Cell-Cycle Times 2 0 Human nerve cells are an example of cells that are permanently in G … M phase (mitosis) Chohesins - link the sister chromatids together APC/C - breaks these interactions and allows the chromatids to separate to opposite poles of the cell High accuracy and fidelity are required to assure that the chromosomes will be segregated properly… checkpoint system to ensure that previous phases are complete before advancing to the next… 3 Concept of The Cell Cycle Control System System based on a variety of related cyclically activated kinases that regulate progression through the cycle by ensuring everything is read for next phase of division at checkpoints… Checkpoints ensure things should proceed:  Is all DNA replicated?  Is cell big enough?  Is environment favorable?  Is DNA damaged? Cell division machinery stops if things go wrong… 4 Roa and Johnson Classic Cell Fusion Experiment (1970) Cell fusion experiments of cells in different phases of the cell cycle were use used to determine if some “diffusible factor” found in the cytoplasm was responsible for progression through the different phases… They Found:  Diffusible factors were indeed responsible for entry into the M & S phases of the cell cycle These Factors Involves 3 protein families… 2 of which are enzymes… i) Kinases  phosphorylate target areas on proteins ii) Phosphatases  dephosphorylate target areas on proteins iii) Cyclins  class of proteins whose levels vary during the different phases of the cell cycle and are a subunit that must bind to CDK to form the active CDK-cyclin heterodimer complex Several organisms were used to study these checkpoint processes as each provided advantages in certain experiments and due to the high conservation of these checkpoint mechanisms in all eukaryotic cells the processes in experimental organisms such as yeast and frogs are relevant to human cells…
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