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The Cell Cycle & The Process of Cell Division Purpose of Mitosis • Growth • Embryonic development • Tissue repair • Asexual reproduction The Role of the Chromosome Chromosomes are a “scaffolding” that hold, carry and protect DNA Chromosomes • Exist as Chromatin for most of the cell cycle • • • – Unwound, string-like (like a stretched out Slinky) – DNA replication and RNA synthesis occur when like this • DNA in each cell is approximately 2 meters long Prior to cell division, Chromatin begins to coil and thicken (super coiling) Now called Chromosomes (sister chromatids) – Initially joined all along their length by proteins called cohesins, later centromere Human somatic cells have 46 chromosomes – Gametes have 23 The Cell Cycle • 2 general periods exist: Interphase and mitotic (M) phase • 22-24 hour cycle – 21 hours of Interphase (Growth) – 1 hour of Mitosis (Division) The Cell Cycle Interphase • 21 hours long • Three Phases – G1, S, & G2 • Cells grow in size • Carries on metabolism ATP synthesis, excretion of waste, new organelle synthesis, new proteins • Chromosomes are duplicated G1 (5-6 hrs long) (a.k.a.-Gap 1) • Rapid growth and metabolic activity • Multitudes of proteins being synthesized • Think “Magic ‘E’ word” S (10-12 hours long) (a.k.a.-Synthesis) • More growth • DNA synthesis/replication G2 (4-6 hrs long) (a.k.a.-Gap 2) • Growth • Centrosomes replicate – In animal cells, each centrosome has 2 centrioles • Organelle manufacturing • Final preparations for cell division G0: Molecular Control of Cell Cycle • Different cells = different cell cycles • Cytoplasmic signals seem to be most valid theory of cell division (think ECM; extra cellular matrix) – Cell cycle control system • Checkpoints dictate “stop and go” – Can be internal and/or external signals • G1 checkpoint seems to be most important – Go = G1, S, G2 and Mitosis – Stop = G0 (Most cells in the human body) Cyclins and Cyclin-Dependent Kinases • Protein kinases (phosphotransferase) – Enzymes that activate or inactivate other proteins • “Go” signal at G1 and G2 checkpoints • Cyclins (think major milestones) – Proteins that attach to kinases – Concentration fluctuates during cell cycle • Cyclin-dependent kinases (Cdks) – Example of this relationship shown in Metaphase to Anaphase conversion …continued • Density-dependent inhibition • • – Release of growth factors or growth inhibiting factors • Surface proteins seem to be the receptors and messengers of this phenomena Anchorage dependence – Substratum is essential for cell division Cancer cells do not respond to these mechanisms – HeLa cells (Henrietta Lacks, 1951) – 20-50 cell divisions is the norm before autophagy – Transformation forms cancer cells • Benign: Does not migrate • Malignant: affects multiple tissues/organs – metastasis Mitosis: Cell Division • Approximately 1 hour long • Has 5 phases – Prophase – Prometaphase – Metaphase – Anaphase – Telophase Prophase • Chromatin thickens into chromosomes (supercoiling) – Sister Chromatids visible • Held together by a centromere • Mitotic spindle begins to form (other microtubles dissociate to help form spindle) Prophase (continued) • Nucleoli disappear • Centrioles migrate to opposite ends of the cell – Spindle begins to form (cage-like structure, “aster”) Prometaphase • Nuclear envelope fragements • Microtubles (spindle makes its way towards nuclear region) • Kinetochore present on each sister chromatid • Microtubels attach to kinetochore and begin to loosen sister chromatids Metaphase • Longest phase of mitosis (20 minutes) • Centrosomes at opposite poles • Spindle arranges the chromosomes at the equatorial plane of cell • Chromosomes are fully attached to micortubles at kinetochore Anaphase • Shortest stage • Sister chromatids separate via cohesin separation • Microtubles begin dissociating, moving chromosomes to poles • Cell lengthens as structural microtubles lengthen Telophase • Chromatids reach opposite ends of the cell • Nucleus and nucleolus form (nucleus via ER) • Chromosomes lengthen into chromatin • • again Spindle breaks down Plasma membrane begins to separate (cytokinesis) – Animal cells pinch (cleavage furrow) – Plant cells form new cell wall Telophase in plant and animal cells Identical Offspring • Asexual reproduction results in offspring “identical” to their parents • Types of asexual reproduction: • Binary Fission • Budding • Spore Formation • Regeneration • Vegetative Reproduction Binary Fission • Parent cell increases in size and splits into two • • • • equal but smaller parts No parent cell is left Occurs in single-celled organisms: amoeba, protozoa and certain algae Prokaryotes (bacteria and archea) divide via binary fission without mitosis One gene containing chromosome – Origin of replication – Cell elongates and separates (tubulin? Actin?) Bacteria & Protozoa Binary Fission Evolutionary Mitosis • Ancestral mechanisms remain intact – Dinoflagellates: Replicated chromosomes attach to nuclear envelope and separate with nuclear division – Diatoms and Yeasts: Spindle within nucleus separates chromosomes