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Transcript
Cellular Reproduction (Mitosis) Anderson Spring 2017 College of the Redwoods Cell Division • Why do cells need to divide? • Single-celled organisms – cell division is their method of reproduction • Make an exact copy of themselves • Little genetic variation (unless mutations occur) • Multicellular organisms – necessary for repair, tissue regeneration, and growth • Ex: Blood and skin cells constantly being produced • Zygote (single cell from egg/sperm fusion) must divide trillions of times to create multicellular organism Genomic DNA • Genome – a cell’s complete complement of DNA • Prokaryotes – one circular double-stranded DNA molecule • Eukaryotes – several linear double-stranded DNA molecules bound with proteins (chromosomes) • Each species has a characteristic number of chromosomes • Each cell has 2 matched sets of chromosomes Species # of total chromosomes # of sets of chromosomes Human 46 23 Cat 38 19 Dog 78 39 Fruit Fly 8 4 Diploid vs Haploid • We use the letter n to represent a single set of chromosomes • Diploid – 2 matched sets of chromosomes, 2n • Humans have 46 total chromosomes in somatic cells (non-sex cells) • Haploid – one set of chromosomes, n • Humans have one set of 23 chromosomes in gametes, or sex cells (egg and sperm) Homologous Chromosomes • Matched pairs of chromosomes in diploid organism DNA wound up tightly Locus 1 • Same length (except X/Y) • Have specific nucleotide segments (gene) in the same location (locus) Genes Locus 2 • Each copy originates from a different parent From Mom From Dad Homologous Pair Cell Cycle • Ordered series of events involving cell growth and cell division (eukaryotes) 2 Phases: 1. Interphase – cell grows and DNA is replicated 2. Mitotic phase – replicated DNA and cytoplasmic contents are separated and cell divides Interphase • Cell undergoing normal processes while preparing for cell division • When cell is not preparing to divide it’s just undergoing normal processes (“resting” state) • G1 Phase (1st gap) • Cell accumulating building blocks of chromosomal DNA and associated proteins • Obtaining enough energy reserves to replicate each chromosome Interphase • S Phase (synthesis phase) • DNA replication • Makes identical copies of each chromosome (sister chromatids) • Firmly attached at centromere • Semi-condensed chromatin configuration (can’t see it under microscope yet) S Phase Cont’d • Centrosome also duplicated • Microtubule bundle that’s part of the cytoskeleton • Centrosomes has pair of centrioles that help organize cell division • The 2 centrosomes make up the mitotic spindle Interphase • G2 Phase (2nd gap) • Cell replenishes its energy stores • Synthesizes proteins necessary from chromosome manipulation • Some organelles are duplicated • Cytoskeleton dismantled to provide resources to mitotic spindle Mitotic Phase • To make 2 daughter cells (make exact copy) • Contents in cell’s nucleus and cytoplasm must be divided • Duplicated chromosomes line up, separate and move to opposite poles 1. Mitosis – 5 state process which accomplishes nuclear division 2. Cytokinesis – physical separation of cytoplasmic components into 2 cells Mitosis 5 Stages of Mitosis 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase Prophase • Nuclear envelope (membrane) starts to break into small vesicles • Golgi apparatus and endoplasmic reticulum fragment and disperse to periphery • Centrosomes begin to move to opposite poles, microtubules extend • Nucleolus disappears • Sister chromatids coil more tightly (visible under microscope) Prometaphase • Remnants of nuclear envelope disappears • Microtubules stretch across former nuclear area • Chromosomes become more condensed • Each sister chromatid attaches to spindle microtubules at centromere via kinetochore (protein complex) Metaphase • Chromosomes align in a plane (metaphase plate) • Midway between the 2 poles • 2 kinetochores of each chromosome attached to microtubule at opposite poles • Spindle checkpoint – ensures chromatids will split evenly Anaphase • Sister chromatids split apart at centromere (now chromosomes again) • Chromosomes pulled toward respective centrosome • Microtubules not attached to chromosome push poles apart to make cell longer Telophase • When chromosomes reach opposite pole they decondense • Mitotic spindles broken down – will be used to build new cytoskeleton • Nuclear envelope forms around chromosomes (both copies) Cytokinesis • Physical separation of cytoplasmic components of 2 daughter cells • Very different for cells with cell wall vs. no cell wall Cytokinesis without Cell Wall • Begins after the onset of anaphase • Contractile ring (actin filaments) form inside along former metaphase plate • Actin filaments pull equator of cell inward forming cleavage furrow • Think of belt around “waist” of cell being pulled tighter until the cells split Cytokinesis with Cell Wall • Rigid cell wall prevents the “belt tightening” • New cell wall must form between the cells • The Golgi vesicles (vesicles contained broken down Golgi apparatus) collect on metaphase plate • Vesicles fuse to form cell plate • Cell plate will grow until it merges with outer cell wall • Accumulated glucose build new cell wall of cellulose G0 Phase • Most of the time, newly formed daughter cells immediately enter interphase followed by mitotic phase • But some cells go into a state of “rest” – not actively preparing to divide • Cells that never or rarely divide remain in G0 permanently Internal Checkpoints • Mistakes in duplication or distribution of chromosomes can lead to mutations that can be passed on to new cells • Checkpoints are internal control mechanisms that can stop the cell cycle during unfavorable conditions • These happen: • Near end of G1 • End of G2 • During metaphase Internal Checkpoints • G1 Checkpoint – determines whether all conditions are favorable for cell division • Point where cell irreversibly commits to cell division • Check for genomic DNA damage • Checks for adequate reserves and cell size • G2 Checkpoint – stops entry into mitotic phase • Cell size and protein reserve is assessed • Most importantly, ensures that all chromosomes have been replicated and DNA is not damaged • M Checkpoint – end of metaphase (spindle checkpoint) • Determines if sister chromatids are correctly attached to spindle microtubules (separation during anaphase is irreversible) What happens when the checkpoints fail? • Even with the checkpoint in the S phase (when DNA gets copied) a small % of replication errors still occur • If the error occurs in a nucleotide sequence of a gene, a gene mutation results • Over and over, small uncorrected errors are passed from parent to daughter cell and accumulate with each generation • If the mutation renders protein nonfunctional, the cell will die • Sometimes a mutation increases cell cycle activity Cancer • Cancer starts when the mutation gives rise to a faulty protein involved in cell reproduction • Uncontrolled growth of mutated cells outpaces growth of normal cells (cell cycle sped up) • Proto-oncogenes – genes that code for positive cell-cycle regulators • Oncogenes – mutated proto-oncogenes that cause cell to become cancerous • Cells can be pushed past their checkpoints to rapidly divide Cyclin-dependent kinase (Cdk) • Cyclins are cell cycle regulators • They bind to Cdk to activate enzymes involved in DNA replication • When a mutation causes Cdk to be activated before it should be, it can push the cell cycle past a checkpoint • Cdk is a protooncogene • Once Cdk is altered to increase rate of cell cycle it becomes an oncogene P53 • Tumor suppressor gene – gene that codes for negative regulator proteins, like P53 • When the genes are activated, uncontrolled cell division can be controlled • Mutated P53 genes have been identified in more than half of all human tumor cells • Damaged P53 allows mutations to continue Prokaryotic Cell Division • Cell division is only method of reproduction for unicellular organisms • Daughter cell becomes new organisms • Since there’s no nucleus or multiple chromosomes, mitosis is unnecessary • Prokaryotes use binary fission for cell division • Like mitosis, all DNA is copied and cytoplasmic contents divided Binary Fission • DNA replication starts at origin and replicates in both directions • Each origin point moves towards cell ends, elongating cell • Septum forms between nucleoids (cell wall) • When new cell walls are in place, the cells separate