1. The Cell Division Cycle
Cell cycle
Cell Division
Mitosis

2. Science Starter Mitosis is going on as we speak in your body.
Do you know which cells are dividing as we speak?

3. Cell Theory 3. All Cells arise only from pre-existing cells
How is this accomplished?
Cell division

4. Cell division is needed for
- Reproduction (mostly unicellular organisms, asexual reproduction in multi-cellular organisms)
- Growth and development of multi-cellular organisms
- Repair, regeneration of tissues in multi-cellular
organisms

5. A multi-cellular organism needs to coordinate cell division across different tissues & organs – lack of coordination= cancer
critical for normal growth, development & maintenance
coordinate timing of cell division
coordinate rates of cell division
not all cells can have the same cell cycle

6. Frequency of cell division varies by cell type
embryo
cell cycle < 20 minute
skin cells
divide frequently throughout life
12-24 hours cycle
liver cells
retain ability to divide, but keep it in reserve
divide once every year or two
mature nerve cells & muscle cells
do not divide at all after maturity
permanently in G0

7. The Cell Cycle Phases R S - Synthesis - DNA replication occurs
M - Mitosis - nuclear division and cytokinesis
Gap phases: G1 prior to S
G2 prior to M G1 S G2 M R
G1, S and G2 collectively called Interphase

9. The Logic of the Mitotic Cell Division Cycle
Goal - Faithful Duplication of the Genetic Material - that is mother and daughter cells are identical genetically
Goal - achieved through highly ordered sequences of events and feed-forward and feed-back links and loops:
an event is dependent on the correct completion of a preceding event;
an event determines the timing and nature of following events;
an event can negatively influence a preceding event - ensuring a forward movement and occurrence of an event only once per cycle (e.g. DNA replication)

10. S - Synthesis phase G2 – Gap phase 2M
S - Synthesis phase
- Cell will duplicate, make an exact second copy of all
it's chromosomes (1 chromosome = 1 molecule DNA)
- This is when DNA Replication takes place
G2 – Gap phase 2
- Cell gets ready to divide
- Checks if all DNA is completely replicated
- Check if there are no errors during Replication

11. Gap phase 1- G1 Occurs after Mitosis, prior to the next S-phase;
Couples growth to cell division;
Major control/decision point in a cell’s life cycle
Is absent/mostly absent in early embryonic cycles G1 S G2 M

12. A Cells life can be viewed as a shifting balance between
the Mitogenic and Anti-mitogenic signals it receives
Signals: Cell-to-cell communication, secreted factors (in the case of tissue cultured cells also from serum) and internal signals.
Mitogenic signals - usually through the MAP kinase signaling pathway - grow and divide
Anti-mitogenic - varry: apoptotic signals; starvation; contact inhibition; differentiation signals…….

13. The Restriction Point A A A R M Apoptosis Differentiation SenescenceG1 S G2 M R
Apoptosis
Differentiation
Senescence
Division M A M A M A
M - mitogenic – generates mitosis – signal to divide
A - anti-mitogenic = opposite of above – don't divide!

14. SPF and MPF
Synthesis promoting factor
Maturation promoting factor

15. Conclusion Molecules present in the cytoplasm
Figure 9.14
G1 nucleus
immediately entered
S phase and DNA
was synthesized.
Experiment
Experiment 1
Experiment 2
Results S M G1
G1 nucleus began
mitosis without
chromosome
duplication.
Conclusion Molecules present in the cytoplasm
control the progression to S and M phases.

16. The Cell Cycle Machinery - Cyclin-dependent Kinases
cdk4,6 D G1 S G2 M R
cdk1 B
cdk2 E
cdk1 A
cdk2 A

17. Cyclins - Name – first discovered due to highly periodic appearance
and disappearance of protein in sea urchins
- Fluctuations in protein levels linked to cell cycle stage
- Genetic evidence for cell cycle regulation (S. cerevisiae and S. pombe), followed by biochemical evidence – yeast and mammals
periodicity is achieved by
control of expression
- transcription
- mRNA stability
- translation
-protein degradation

18. Cyclin-CDK = 2 protein complex

19. Cycling of CDK activity
The cell cycle is ‘driven’ by fluctuations in Cyclin-CDK activity
Cyclin-CDK activity is regulated in several ways:
Cyclin protein abundance (transcription, translation, protein degradation)
CDK phosphorylation (inhibitory and activating)
Cyclin-CDK complex assembly
CDK inhibitors

20. Distinct CDKs drive different transitions

21. CDK-regulated events are.....
Mitotic CDK disappears at the end of Mitosis until the next
G2 phase = You can't do Mitosis until you have done G1 and S phase – why?

22. MPF activity ensures One-way progression

23. Stages of Mitosis
1. Interphase/Early Prophase – chromosomes look like tangled rope, no individual chromosomes are visible – not condensed
2. Prophase – chromosomes condense – DNA gets packaged tightly with the help of proteins, we clearly see the chromosomes – they have a shape; nuclear membrane falls apart, breaks down – centrioles move to opposite ends of cell

24. Prophase

25. Metaphase - Spindle fibers (come out of centrioles) – like ropes with
hooks will attach to
the chromosomes and pull
them to the middle of the
cell – the metaphase plate
- The two identical pairs of
chromosomes are sticking together –
they are called sister chromatids

26. Anaphase - The spindle fibers contract (similar to muscles)
- The glue holding the two
identical chromosomes (sister
chromatids) breaks down
- The two sister chromatids are
pulled by the spindle fibers to
opposite ends of the cell

27. Telophase - Chromosomes have moved to opposite ends
-Nuclear membrane re-forms
around "new" chromosomes
- Cell begins Cytokinesis – it
pinches in in preparation for
splitting

28. Cytokinesis - The Cytoplasm and all its content divides in two
- Cell division is complete:
2 new, daughter cells are
formed
- The daughter cells have
identical chromosomes/DNA

29. Two sister chromatids of
Figure 9.7a
10 m
G2 of Interphase
Prophase
Prometaphase
Chromosomes
(duplicated,
uncondensed)
Early mitotic
spindle
Centromere
Fragments
of nuclear
envelope
Centrosomes
(with centriole
pairs)
Nonkinetochore
microtubules
Aster
Figure 9.7a Exploring mitosis in an animal cell (part 1: G2 of interphase through prometaphase)
Plasma
membrane
Nucleolus
Kinetochore
Kinetochore
microtubule
Nuclear
envelope
Two sister chromatids of
one chromosome 29

30. Telophase and Cytokinesis
Figure 9.7b
10 m
Metaphase
Anaphase
Telophase and
Cytokinesis
Metaphase
plate
Cleavage
furrow
Nucleolus
forming
Figure 9.7b Exploring mitosis in an animal cell (part 2: metaphase through cytokinesis)
Nuclear
envelope
forming
Spindle
Centrosome at
one spindle pole
Daughter
chromosomes 30

31. Two sister chromatids of
Figure 9.7c
G2 of Interphase
Prophase
Centrosomes
(with centriole
pairs)
Chromosomes
(duplicated,
uncondensed)
Early mitotic
spindle
Centromere
Aster
Figure 9.7c Exploring mitosis in an animal cell (part 3: G2 of interphase and prophase)
Plasma
membrane
Nucleolus
Nuclear
envelope
Two sister chromatids of
one chromosome 31

32. Prometaphase Metaphase Fragments of nuclear envelope Nonkinetochore
Figure 9.7d
Prometaphase
Metaphase
Fragments
of nuclear
envelope
Nonkinetochore
microtubules
Metaphase
plate
Figure 9.7d Exploring mitosis in an animal cell (part 4: prometaphase and metaphase)
Kinetochore
Kinetochore
microtubule
Spindle
Centrosome at
one spindle pole 32

33. Telophase and Cytokinesis
Figure 9.7e
Anaphase
Telophase and
Cytokinesis
Cleavage
furrow
Nucleolus
forming
Figure 9.7e Exploring mitosis in an animal cell (part 5: anaphase, telophase and cytokinesis)
Nuclear
envelope
forming
Daughter
chromosomes 33

34. G2 of Interphase 10 m Figure 9.7f
Figure 9.7f Exploring mitosis in an animal cell (part 6: G2 of interphase micrograph)
G2 of Interphase 34

35. Figure 9.7g
10 m
Figure 9.7g Exploring mitosis in an animal cell (part 7: prophase micrograph)
Prophase 35

36. Prometaphase 10 m Figure 9.7h
Figure 9.7h Exploring mitosis in an animal cell (part 8: prometaphase micrograph)
Prometaphase 36

37. Figure 9.7i
10 m
Figure 9.7i Exploring mitosis in an animal cell (part 9: metaphase micrograph)
Metaphase 37

38. Figure 9.7j
10 m
Figure 9.7j Exploring mitosis in an animal cell (part 10: anaphase micrograph)
Anaphase 38

39. Telophase and Cytokinesis
Figure 9.7k
10 m
Figure 9.7k Exploring mitosis in an animal cell (part 11: telophase and cytokinesis micrograph)
Telophase and
Cytokinesis 39

40. Remember the Direction

41. Mitotic Cyclin is degraded AFTER Chromatids split and move apart

42. The Cell Cycle - Sequence of the phases in the life of a cell
- Has 4 phases: G1
S these 3 are
G2 called
Interphase
M - Mitosis

43. Asexual Reproduction Reproduction with one parent
Offspring are genetically identical to the parent
Binary fission: type of asexual reproduction
Organism splits in half to become two new identical organisms
Cloning: production of identical genetic copies of a parent
Plants reproduce this way using mitosis

44. Asexual Reproduction Regeneration: type of asexual reproduction
Star fish can loose an arm and regenerate a whole starfish; planaria – a type of worm
Budding: type of asexual reproduction
Yeast, sponges and hydra can reproduce this way
A new small individual begins to grow out of the side of the parent organism
This is called a bud
The bud breaks free when it is large enough to live on its own

45. Budding Yeast
Fission Yeast

47. Checkpoints
Checkpoint – checking that an even is completed BEFORE proceeding to the next event OR checking for damage/defects
Checkpoint – triggered only when something is wrong
Checkpoints – several – at different places in the cell cycle

48. What happens when a Checkpoint is triggered?
Cell division stops – cell cycle arrest (temporary) and cell attempts to correct problem OR
Cell undergoes apoptosis (programmed cell death) – damage is too extensive
Arrested cells will eventually proceed with cell cycle

49. Mitotic Checkpoints

50. Unusual Cell cycles
Endoreduplication cycles - alteranting S-phases without
intervening mitoses - poliploid cells
2. Embryonic cell division - rapid cycles without/with short
Gap phases - S-M-S-M……- non-cell cycle regulated CDK
activity (constant) - the appearance of G1 probably
signals the beginning of cellular differentiation