1. The Cell Cycle
CELL

2. Overview of Cell Cycle Events

3. Mutants that Arrest the Cell Cycle

4. S. pombe Cell Cycle Mutants

5. Wee1 & Cdc25 wee1 kinase Cdc25 phosphatase inhibits Cdk1-cyclinB in G2
mutation allows progression into mitosis without growth
Cdc25 phosphatase
promotes G1 S transition
mutation prevents DNA replication and mitosis

6. Cell Cycle Progression Regulated by Cdks and Cyclins

7. Regulation Run Amok

8. 18.1-Cdk2.mov

9. Cdk-Cyclin Activities During the Cell Cycle

10. G1-S Restriction Point

11. Regulation of Transcription of Key Cell Cycle Progression Genes by Rb & E2F during G1

12. External Signals Ultimately Trigger Phosphorylation of Rb

13. Aberrations in Cell Cycle Control Proteins Lead to Cancer

14. G1-S Transition Cdk4/6-cycD P-pRb PpRb releases E2F E2F txbs CycsA & E
Cdk2-cycE spike triggers S-phase

15. G1-S Checkpoint And S-Phase Considerations
Replication should not begin if DNA is damaged
DNA integrity monitored by
p53 induced genes
The p53 conundrum
too little – bad
too much - bad

16. p53 & Mdm2 in G1-S Checkpoint
Ubiquination of p53
Maintains level of p53
p53
P’ated in response to damaged/unreplicated DNA
Mdm2 doesn’t bind P’ated p53
P-p53 activates apoptosis

17. S-Phase Controls Replication must occur only 1 time / cell cycle
Origin “licensing”
ORC – origin recognition complex
SPF – S-phase promoting factor
Mcms
helicases that are only loaded once

18. Regulation by Phosphorylation
CAKs P’ate T161 of T loop to activate
Wee1/Myt1/Mik1 P’ate T14 & Y15 to inactivate
Cdc25 deP’ates T14 & Y15 to activate

19. Nuclear Localization of Cdk1-cycB1 Occurs at G2/M Transition
Cdk1 cytoplasmic , cyclinB1 shuttles, Cdk1-cycB1 shuttles
At end of G2 P’tion of CycB1nuclear export signal when complexed to Cdk1
CycB1 carries Cdk1 into nucleus
Cdk1-cycB1 then trapped within nucleus
Activated by deP’tion of T14 & Y15 by Cdc25

20. Activation of Cdk1-cyclin Requires Inactivation of Cdk2-cyclinA

21. G2 Checkpoint
Is DNA replication complete
Is DNA undamaged