1. Lecture 15 - Mitosis

2. M for mitosis

3. Mitosis is the process that partitions replicated chromosomes equally to 2 daughter cells

4. Mitosis proceeds through 6 stages
Cytokinesis

5. 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

6. Interphase - late G2 DNA is duplicated Cell has doubled in size
Centrosome has duplicated
M-cyclin levels high

8. Prophase Chromosomes condense Nuclear envelope breaks down
Microtubules reorganize to make asters
Centrosomes move to opposite sides of the cell

9. Replicated chromosomes are prepared for segregation by cohesins and condensins
Cohesins hold sister chromatids together
Cohesins are deposited on chromosomes during S-phase

10. 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

11. The nuclear envelope breaks down and re-forms during mitosis

12. Dynamics of the nuclear envelope during cell division

13. 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

14. Centrosomes organize the microtubules in a mitotic spindle

15. Microtubules are the core structural component of the mitotic spindle

16. Changes in microtubule dynamics contribute to spindle assembly
Interphase
Mitosis
Growth rate
Intermediate
Low
Shrinkage rate
High
Frequency of catastrophe

17. Three sets of microtubules make up the mitotic spindle

18. 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

19. 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

20. Kinetochores attach chromosomes to the mitotic spindle

21. Capture of centrosome microtubules by kinetochores

22. 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

23. Unattached kinetochores mediate the mitotic checkpoint

24. 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

25. 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

26. APC triggers the separation of sister chromatids by tagging cohesins for destruction

27. Anaphase chromosome movement is driven by 2 processes

28. Spindle elongation during anaphase B is mediated by motor proteins

29. Microtubule attachment sites in a kinetochore are thought to form a sliding collar

30. Kinetochore movement at the metaphase-to-anaphase transition

31. 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

32. Cytokinesis
The division of the cytoplasm is completed by the contractile ring
Cells re-enter interphase in G1
Microtubules reform their interphase organization

33. 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.

34. The contractile ring divides the cell in two

35. Organelles are segregated to each daughter cell during mitosis

36. Golgi apparatus partitioning during mitosis