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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
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THE CELL CYCLE IPMAT Regulation & Its Lifespan Implication
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 • Centrosomes • plant & animal cells • AKA MTOC’s www.cellsalive.com 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
The Cell Cycle 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/N100/2k4ch8mitosisnotes.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
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
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.html
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 anti-aging powers of telomerase w/o risk of cancer NO EASY TASK
Telomeres 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