Cancer Biology 134

1. The Cell Cycle
Chapter 8:
Karobi Moitra (Ph.D)
pRb and Control of the NCI Frederick , NIH
Cell Cycle Clock Cancer Inflammation Program
Human Genetics Section
Copyright © Garland Science 2007 Frederick MD.

2. The cell cycle is a programmed
series of events that enables
a cell to duplicate its contents
and generate 2 daughter cells

3. The Cell Cycle
Resting stage
Gap2
Gap 1
Synthesis
Figure 8.3b The Biology of Cancer (© Garland Science 2007)

4. The mitotic cell cycle in newt lung cells
Anaphase:
Chromosome
Prophase: halves are
Chromosomes pulled apart
Condense (blue)
Telophase:
Chromatids
Prophase: decondense
Centrosomes and nuclear
begin to assemble membrane
(green) forms
Metaphase:
Chromosomes
align and attach
to spindle fibres
Figure 8.3a The Biology of Cancer (© Garland Science 2007)

5. Checkpoint Control

6. Checkpoint Control
Checkpoint controls in the cell cycle ensure that
a new step in the cycle is not undertaken until
the preceding step has been completed.

7. Cell Cycle Checkpoints : Quality Control
Figure 8.4 The Biology of Cancer (© Garland Science 2007)

8. What happens if a damaged cell overrides
these checkpoints?

9. Cancer is associated with abnormal cellular
proliferation
Cells divide when they should not divide and they
lack the normal control systems to shut off unwanted
cell division

10. Cancer Cells May Lose Checkpoint Controls
Cell death

11. Loss of checkpoint controls result in altered Karyotype
Normal human Rad17 deprived
(Rad17 prevents
rereplication)
Figure 8.5a The Biology of Cancer (© Garland Science 2007)

12. Chromosome breaks in cells Lacking ATR
(ATR can stall replication to repair breaks)
ATR: ataxia telangiectasia and Rad3 related protein
Figure 8.5c The Biology of Cancer (© Garland Science 2007)

13. Once a Cell Advances beyond R- restriction point it
is committed to advance through the cell cycle and
divide
Go to M
Remain in G1
Go to G0
Figure 8.6 The Biology of Cancer (© Garland Science 2007)

14. Restriction Point :
G1 phase checkpoint in the cell cycle of
animal cells

15. The Cell Cycle Clock controls the cell cycle
Figure 8.1 The Biology of Cancer (© Garland Science 2007)

16. Table 8.4 The Biology of Cancer (© Garland Science 2007)

17. Each cyclin pairs with a specific cyclin dependent
kinase (CDK) to carry out the steps in the cell cycle
Figure 8.8 The Biology of Cancer (© Garland Science 2007)

18. Cyclin +cyclin-dependent kinase (CDK)
+ CAK = active complex

19. Coordinated cyclin levels during the cell
cycle : levels of different cyclins change
at different stages in the cell cycle
Figure 8.12 The Biology of Cancer (© Garland Science 2007)

20. Table 8.1 The Biology of Cancer (© Garland Science 2007)

21. Prevents
damaged cells
to proceed with
the cell cycle and also
causes interchange of CDKs
at different stages of the
cell cycle
CDK inhibitors block the action of CDK’s at various points
in the cell cycle
p - designation of a tumor suppressor gene
Figure 8.13a The Biology of Cancer (© Garland Science 2007)

22. pRB and cell cycle control

23. The E2F transcription factor

24. Transcription factors can turn genes ‘on’

25. E2F is a transcription factor which can switch on genes
that can cause cell division. Rb can inactivate E2F.

26. Mutations inactivate pRb, p16 (TSG’s)
& the abnormal cell replicates

27. How can knowledge of the cell cycle can be utilized to
develop anticancer drugs?

28. The cell cycle is a programmed series of events that
enables a cell to duplicate its contents
and generate 2 daughter cells
Checkpoint controls in the cell cycle ensure that
a new step in the cycle is not undertaken until
the preceding step has been completed.
Many types of cancer cells have inactivated
one or more of these checkpoint controls to propel
neoplastic growth.