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Unit 9 – Cell cycle Overivew.docx

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BIOL 130
Heidi Engelhardt

BIOL 130 Unit 9 – Cell cycle, Mitosis, Meiosis Key Concepts  Cell division involves an orderly sequence of events in which cell duplicates its content and divides into two – “cell cycle”  Details of cell cycle vary with organisms, and different time in an organism’s life  Unicellular = generates complete new organism (bacteria, yeast, protozoa)  Metazoans = many cell divisions required to generate new organism from fertilized egg Certain Features of cell division are universal  Must faithfully replicate DNA  Replicated DNA must be accurately distributed (segregated) to daughter cells  Most cells also duplicate their other macromolecules and organelles and double in size before they divide Eukaryotes: Mitosis Vs. Meiosis  Mitosis o Division of genetic material that produces daughter cells genetically identical to parent cell o Usually accompanied by cytokinesis, division of the cytoplasm into the two daughter cells  Meiosis o Division of genetic material to produce daughter cells with half the hereditary material found in the parent cell o Involved only in the production of gametes (eggs and sperm) o Basis of sexual reproduction and genetic inheritance Eukaryotic Chromosomes  Multiple linear chromosomes housed in nucleus  Two copies of each essential to survive  Highly variable in number (1 - >500 pairs) o Humans 2n=46 o Chrms # not correlated with complexity  Complex packaging of DNA  Typical human chrms 140 million nucleotides long – 5cm if laid out straight DNA packaging in Eukaryotes  DNA double helix wrapped around histone proteins  Tightly packed DNA w/ histones  Chrms extended form  Condensation in preparation for mitosis/meiosis  Entire mitotic chromosome BIOL 130 Homologous Chromosomes vs. Sister Chromatids  Homologs = one from each parent  Replicated homolog = considered one chromosome consisting of two sister chromatids Phases of the Cell Cycle  Interphase – 90% of a proliferating cell’s time o Cell grows, produces proteins and organelles, copies its DNA, prepares for cell division  G1Phase (Gap 1) – most of a cell’s growth  S Phase (synthesis) – DNA copied  G Phase (Gap 2) – cell completes preparations for mitosis 2  M Phase – Mitosis and cytokinesis o Subdivided according to state of chrms Two Transient cytoskeleton structures are required for mitosis in animal cells  Microtubules of the mitotic spindle  Actin and myosin filaments of the contractile ring Stages of Mitosis  G2of interphase – preparation for mitosis  Prophase –  Prometaphase  Metaphase – chromosomes migrate to ‘equator’ of cell (metaphase plate)  Anaphase – sister chromatids separate  Telophase & Cytokinesis – nuclear envelope re-forms; spindle apparatus disintegrates Cytokinesis: Animals Vs. Plant Cells  Animal – involves ring of actin filaments just under plasma membrane, in association with motor proteins (myosin)  Plant – new wall must be constructed between dividing plant cells o Microtubules and proteins define and organize the regions where new cell membrane and wall will form o Vesicles from Golgi arrive, carrying polysaccharides and glycoproteins to lay don matrix for new cell wall o Later cellulose fibres are laid down to complete wall Do all cells go through the cycle continuously? Is the length always the same?  Depends on cell type, developmental stage, external signals o Some cells divide continuously at high rate  Epithelial linings of intestine – couple times per day  Some cells do not divide at all once mature – neurons  Early embryos divide more quickly (G1 phase skipped/reduced) – invertebrate – 20-30 hrs. /mammalian ~ 13 hrs. BIOL 130 Control of the Cell Cycle  Factor discovered in mammalian cells that induced mitosis o Subsequently shown to induce mitosis in all eukaryotic cells – mitosis-promoting factor (MPF)  MPF is hetero dimeric protein o Cyclin-dependent kinase (Cdk) – catalytic subunit, transfers phosphate from ATP to certain AAs on target proteins  Not active unless bound to cyclin partner  Levels are constant o Cyclin – regulatory subunit  Levels oscillate throughout the cell cycle o Phosphorylate chromosomal proteins – initiate M phase o Phosphorylate nuclear lamins – initiate nuclear envelope breakdown o Phosphorylate microtubule-associated proteins – activate mitotic spindle o Phosphorylate an enzyme that degrades cyclin – cycle conc. Decline  Four main classes of Cyclins drive the cell cycle o G1-Cdk = help with passage through restriction point o G1/S-Cdk = commit cells to DNA replication o S-Cdk = carry out replication o M-Cdk = promote events of mitosis (aka MPF)  Some cells opt out of the cell o Some cells divide very slowly (if at all), but can be induced to re-enter cell cycle o Some cells become highly specialized and can no longer divide – ‘terminally differentiated’  How do the cell ‘decide’ whether to proceed through the cell cycle? o Should I divide? – External signal received? NO- stay in G 0 o Am I ready to under go mitosis? – DNA properly replicated? No – halt cell cycle and fix it – Can’t be fixed? Cell death o Am I ready to complete mitosis? – All chrms properly attached to spindles? No – halt mitosis and fix it ‘metaphase arrest’ o Molecular Brakes  G 1 damaged DNA/unfavourable extracellular environment  S = damaged or incompletely replicated DNA  G 2 damaged or incompletely replicated DNA  M = chrms improperly attached to mitotic spindle  G1/S checkpoint: Restriction Point o Discovered in yeast o Integration of external & internal signals:  Nutrition / size of cell / DNA undamaged? o Are external signal molecules telling the cell to divide?  In animals, normal cells depend on extracellular space to trigger cell division – no signal to divide = should stay in 0 BIOL 130  Inappropriate ‘start’ signals or progression in the absence of a signal often associated with cancer cells  ENTER IN S PHASE  G2/M checkpoint o Checking for internal issues:  DNA properly replicated? DNA undamaged? Activated MPF present?  ENTER MITOSIS  Spindle Checkpoint (Metaphase > Anaphase) o Have all chrms moved to the metaphase plate? o Are they all aligned? All attached to the mitotic spindle? o Prometaphase – chrms attached to spindle o Metaphase – chrms gathered at metaphase plate o Anaphase – sister chrms pulled apart o PULL DUPLICATED CHRMS APART Cancer  Failure to respect checkpoint  Cell division in the absence of signal/inappropriate start signals  Failure to induce death of damaged cell/dividing de
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