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UNC-Chapel Hill BIOL 205 - Lecture 15 - Mitosis

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02.23.11Lecture 15 - MitosisM for mitosisMitosis is the process that partitions replicated chromosomes equally to 2 daughter cellsMitosis proceeds through 6 stagesCytokinesisSuccessful mitosis requires the precise coordination of many processes• Packaging of the genome into mitotic chromosomes• Regulation of microtubules and motors to build spindle• Disassembly of the nuclear membrane• Attachment and movement of chromosomes on the spindle• Cleavage of a cell into 2 daughtersInterphase - late G2 • DNA is duplicated• Cell has doubled in size• Centrosome has duplicated• M-cyclin levels highProphase• Chromosomes condense• Nuclear envelope breaks down• Microtubules reorganize to make asters• Centrosomes move to opposite sides of the cellReplicated chromosomes are prepared for segregation by cohesins and condensins• Cohesins hold sister chromatids together• Cohesins are deposited on chromosomes during S-phaseReplicated chromosomes are prepared for segregation by cohesins and condensins• Condensins bind to chromosomes in prophase• Molecular motors that “wind” chromatin into small physical packets for mitosisThe nuclear envelope breaks down and re-forms during mitosisDynamics of the nuclear envelope during cell divisionPrometaphase• Chromosomes are captured by microtubules at the kinetochore• Chromosomes undergo active movement oscillating back and forth on the spindle• Kinetochores of each sister chromatid captured by microtubules from each poleCentrosomes organize the microtubules in a mitotic spindleMicrotubules are the core structural component of the mitotic spindleChanges in microtubule dynamics contribute to spindle assemblyInterphaseMitosisGrowth rateIntermediateLowShrinkage rateIntermediateHighFrequency of catastropheLowHighThree sets of microtubules make up the mitotic spindleBipolar spindles are formed by the selective stabilization of interacting microtubules• Microtubules grow in random directions• Overlapping microtubules from opposite poles are cross-linked and stabilized by MAPs and motor proteinsMicrotubule dynamics are regulated by associated proteins• Microtubule-associated proteins (MAPs) stabilize microtubules in interphase, but are phosphorylated in mitosis and decrease their stabilizing effects• Catastrophins are proteins that destabilize microtubules, their activity is upregulated upon entry into mitosisKinetochores attach chromosomes to the mitotic spindleCapture of centrosome microtubules by kinetochoresMetaphase• Chromosome congression to the metaphase plate• Paired kinetochore microtubules on each chromosome are attached to opposite poles of the spindle• Mitotic checkpoint ensures the fidelity of this bi-polar attachmentUnattached kinetochores mediate the mitotic checkpointCheckpoint: spindle assembly • Mitosis must not complete unless all the chromosomes are attached to the mitotic spindle• Mitotic checkpoint delays metaphase to anaphase transition until all chromosomes are attached• Prolonged activation of the checkpoint -->cell death• Mechanism of many anti-cancer drugsAnaphase• M-cyclin is destroyed• Paired chromatids simultaneously separate to form 2 daughter chromosomes• Each chromosome is pulled to the pole to which it is attached• Kinetochore MTs shorten - anaphase A movement• Spindle elongates - anaphase B movementAPC triggers the separation of sister chromatids by tagging cohesins for destructionAnaphase chromosome movement is driven by 2 processesSpindle elongation during anaphase B is mediated by motor proteinsMicrotubule attachment sites in a kinetochore are thought to form a sliding collarKinetochore movement at the metaphase-to-anaphase transitionTelophase• The 2 sets of chromosomes arrive at the spindle pole and begin to decondense• Nuclear envelope begins to reform• Cleavage furrow begins to form around circumference of the middle of the 2 daughter cellsCytokinesis• The division of the cytoplasm is completed by the contractile ring• Cells re-enter interphase in G1• Microtubules reform their interphase organizationCytokinesis is the process by which the cytoplasm is cleaved in twoThe cleavage furrow of the plasma membrane is formed by the action of the contractile ring.The contractile ring divides the cell in twoOrganelles are segregated to each daughter cell during mitosisGolgi apparatus partitioning during


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UNC-Chapel Hill BIOL 205 - Lecture 15 - Mitosis

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