02.23.11 Lecture 15 - Mitosis
Dec 20, 2015
02.23.11Lecture 15 - Mitosis
M for mitosis
QuickTime™ and a decompressor
are needed to see this picture.
Mitosis is the process that partitions replicated chromosomes equally to 2
daughter cells
Mitosis proceeds through 6 stages
Cytokinesis
Successful 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 daughters
Interphase - late G2
• DNA is duplicated• Cell has doubled in
size• Centrosome has
duplicated• M-cyclin levels high
Prophase
• Chromosomes condense
• Nuclear envelope breaks down
• Microtubules reorganize to make asters
• Centrosomes move to opposite sides of the cell
Replicated chromosomes are prepared for segregation by cohesins and
condensins
• Cohesins hold sister chromatids together
• Cohesins are deposited on chromosomes during S-phase
Replicated 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 mitosis
The nuclear envelope breaks down and re-forms during mitosis
Dynamics of the nuclear envelope during cell division
QuickTime™ and aSorenson Video decompressorare needed to see this picture.
Prometaphase
• 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 pole
Centrosomes organize the microtubules in a mitotic spindle
Microtubules are the core structural component of the mitotic spindle
Changes in microtubule dynamics contribute to spindle assembly
Interphase Mitosis
Growth rate Intermediate Low
Shrinkage rate Intermediate High
Frequency of catastrophe
Low High
Three sets of microtubules make up the mitotic spindle
Bipolar 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 proteins
Microtubule 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 mitosis
Kinetochores attach chromosomes to the mitotic spindle
Capture of centrosome microtubules by kinetochores
Metaphase
• 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 attachment
Unattached kinetochores mediate the mitotic checkpoint
Checkpoint: 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 drugs
Anaphase
• 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 movement
APC triggers the separation of sister chromatids by tagging cohesins for destruction
Anaphase chromosome movement is driven by 2 processes
Spindle elongation during anaphase B is mediated by motor proteins
Microtubule attachment sites in a kinetochore are thought to form a sliding collar
QuickTime™ and aH.264 decompressor
are needed to see this picture.
Kinetochore movement at the metaphase-to-anaphase transition
Telophase
• 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 cells
Cytokinesis
• The division of the cytoplasm is completed by the contractile ring
• Cells re-enter interphase in G1
• Microtubules reform their interphase organization
Cytokinesis is the process by which the cytoplasm is cleaved in two
The cleavage furrow of the plasma membrane is formed by the action of the contractile ring.
The contractile ring divides the cell in two
Organelles are segregated to each daughter cell during mitosis
QuickTime™ and aPhoto - JPEG decompressor
are needed to see this picture.
Golgi apparatus partitioning during mitosis