2. Cyclin Bistability (2) Cdk P P Wee1 P CAK Cdc25 Plk1

3. Polo-like kinase-1 (1) Polo-box domain linker domain kinase domain P P T210 P P

4. Polo-like kinase-1 (2) Polo-box domain Wee1/Cdc25C Cdc25C Active E2 Rbx1 Cul1 β -TrCP Skp1 Cyclin B Cdk P kinase domain P P T210 P P P Wee1 Ub Ub Ub Ub Ub Ub

5. CyclinB Checkpoints (1) Checkpoint control? Cdk1 P P Wee1 P CAK Cdc25 Plk1

6. G1 S M G2 Checkpoints (2) DNA damage G1 arrest DNA damage G2 arrest Improper chromosome attachment M arrest Incomplete DNA replication S phase arrest

7. Wee1 p p inactive (G2) active (mitosis) Cdc25A Cdc25B DNA damage (UV, DSB, stalled fork) p21 How is the cell cycle machinery reactivated? G2 checkpoint CycB Cdk1 CycB Cdk1 14-3-3 Cdc25C ATM ATR Chk1 Chk2 p53 Plk1 Plk1 P P

8. 9 1 1 ATR Cell Cycle Restart Plk1 controls recovery Plk-1 Chk Chk P Cell Cycle Arrest Wee1 caffeine

9. 9 1 1 ATR Claspin (1) Claspin Chk Chk P Cell Cycle Arrest

10. 9 1 1 ATR Cell Cycle Restart Plk1 controls checkpoint silencing Plk1 activation? Claspin Plk-1 Chk Chk P Cell Cycle Arrest Wee1

11. 9 1 1 ATR Plk-1 Mitotic entry after DNA damage Claspin Chk Chk P Cell Cycle Arrest Wee1 AurA Bora Cyclin B Cdk1 P P P Cyclin B Cdk1 P

12. CycB Cdk1 P P Plk1 Polo-like kinase-1 and mitotic entry T210 G2 phase M phase Bora P Wee1 Cdc25 Aurora A P P P