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THE CELL CYCLE IPMAT Regulation & Its Lifespan Implication Why Do Cells Divide? Why Do Cells Divide? Reproduction – Binary Fission in bacteria Tissue Growth – Growth in multicellular organisms = more cells not larger cells Tissue Repair Maintain High Surface Area:Volume – High volume = low efficiency Parts in the Process: Chromosomes http://anatomy.iupui.edu/courses/histo_D502/D502f04/lecture.f04/cell.f04/cellf04.html http://mbbnet.umn.edu/icons/chromosome.jpeg Parts in the Process: Centrioles & The MTOC http://sparkleberrysprings.com/v-web/b2/images/lotc/centriole14.jpg Parts in the Process: Spindle Fibers & Kinetochores http://www.nikonsmallworld.com/gallery.php?grouping=year&year=2004&imagepos=18 Parts in the Process Centrioles – animal cells only – MT – spindle fiber organization www.cellsalive.com Centrosomes – plant & animal cells – AKA MTOC’s http://osumolgen.siteturbine.com/sites/osumolgen/images/met3.jpg Parts in the Process Chromosomes – Super-coiled DNA – centromeres Spindle Fibers – MT’s attached to centromeres @ kinetochore – Tracks for chromosome movement toward centrioles @ poles http://www2.geneticsolutions.com/PageReq?id=3844:1873 http://www2.geneticsolutions.com/PageReq?id=3844:1873 The Cell Cycle Interphase can be divided into 3 main substages: – G1 – Gap 1 - period of growth – S – Synthesis – DNA is copied (synthesized) – G2 – Gap 2 – preparation for division The Cell Cycle (continued) Following G2 of Interphase, mitosis (M-phase) carries out division: – Prophase – Metaphase – Anaphase – Telophase & Cytokinesis http://www.biology.iupui.edu/biocourses/N100/2k4ch8mit osisnotes.html Prophase Centrosomes to poles Nuclear membrane disappears Chromatin condenses to form chromosomes http://micro.magnet.fsu.edu/micro/gallery/mitosis/lateprophase.html http://www.dundee.ac.uk/biocentre/GRE%20Scientific%20images/pages/Prophase.htm Metaphase Chromosomes in middle of cell Spindle fibers form Kinetochores attach to centromeres of each chromatid http://www.brown.edu/Courses/BI0020_Miller/images/metaphase-1.jpg http://www.pc.vccs.edu/biology-labmanual/lab7mitmei/whitefishmeta.jpg Anaphase Sister chromatids separate Chromatids move to poles using retreating spindle fibers (D.I.) http://micro.magnet.fsu.edu/micro/gallery/mitosis/earlyanaphase.html http://content.answers.com/main/content/wp/en/thumb/3/38/300px-Anaphase-flourescent.jpg Telophase & Cytokinesis Telophase complete division of nucleus – Spindle fibers disappear – Nuclear membranes reappear Cytokinesis complete division of cytoplasm – Cleavage furrow in animals – Cell plate in plants Plant Animation Animal Mitosis http://iknow.net/CDROMs/cell_cdrom/index.html http://www.cbp.pitt.edu/faculty/yong_wan/index.html Asymmetric Division Specialization of stem cells New daughter cells not identical http://labshelf.com/stem-cells-treatments-research.html http://labshelf.com/stem-cells-treatments-research.html Regulation of Cell Cycle G0 Checkpoints Apoptosis – Damage Prevention – Developmental Oncogenes – Mitosis accelerators Tumor Suppressor Genes – Mitosis brakes G0 – Exit From the Cell Cycle temporary (wbc’s) or permanent (nerve) Cancer cells do not ever enter G0 Checkpoints in the Cell Cycle G1, S, and M occur when cyclins (proteins) bind & activate kinases. Kinases phosphorylate compounds necessary for division. kinases blocked if damage detected @ G1, S, or M checkpoints. MAD p53 ATM http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellCycle.html DNA Damage Detection G1 – p53, a tumor suppressor, checks for damage before DNA replication – If damage cannot be repaired, p53 sends cell to to die so it cannot lead to cancer – P53 mutations implicated in > ½ of all human cancers S – ATM detects DNA damage, helps p53 send irreparably damaged cells to death, & maintains telomere length M – MAD stops mitosis if problems w/ microtubles in spindle fiber formation APOPTOSIS Programmed Cell Death Definition Mechanism of normal, controlled death by: – DNA fragmentation – Cytoplasm shrinkage – Membrane blebbing Cellular “suicide” No spillage or damage to nearby cells No inflammatory response http://www.sgul.ac.uk/depts/immunology/~dash/apoptosis/apoptosisvideo.ht ml Is All Cell Death Equal? Necrosis – Messy cell death usually due to injury – Cellular “homicide” – Cell contents come spilling out leading to an inflammatory response. • Swelling • Redness • Fever Why Suicide? Development – Mouse paws (and human hands) use cell death to form digits. Death As A Necessity For Life Immune system cells • Virally infected cells • Immune cells that don’t recognize “self” • Removal of cytotoxic T cells after infection is conquered DNA damaged cells • Sent to their death by p53 to prevent tumors Disorders Involved Neurological disorders such as Huntington’s, Parkinson’s and Alzheimer’s diseases • Too much apoptosis Cancer • Not enough apoptosis Cell Division Cell Death Genes in Cancer Oncogenes – Genes known to speed up mitosis – Mitosis accelerators when ON (phosphorylation) – Cancer results if ON when should be OFF Tumor Suppressor Genes – Mitosis brakes – Tumors result if OFF when should be ON Can a Cell Divide Forever? Normal Cells – NO – Telomeres, buffer zones @ tips of each chromosome, get shorter w/ each division – Cells die when telomeres gone • EX: Aging effects are due to dead cells that can no longer be replaced Can a Cell Divide Forever? Cancer Cells – YES – Telomerase is ON • Enzyme repairs telomeres after each division Embryonic Stem Cells – YES – Fountain of Youth lies in harnessing antiaging powers of telomerase w/o risk of cancer NO EASY TASK www.hybridmedicalanimation.com http://www.ellisonfoundation.org/images/pfbs/p018_telomeres.jpg The Cell Cycle http://bhs.smuhsd.org/bhsnew/academicprog/science/vaughn/Student%20Projects/Paul%20&%20Marcus/Cell_Replication.html