College Medema 2

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College Medema 2

  1. 2. Cyclin Bistability (2) Cdk P P Wee1 P CAK Cdc25 Plk1
  2. 3. Polo-like kinase-1 (1) Polo-box domain linker domain kinase domain P P T210 P P
  3. 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
  4. 5. CyclinB Checkpoints (1) Checkpoint control? Cdk1 P P Wee1 P CAK Cdc25 Plk1
  5. 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
  6. 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
  7. 8. 9 1 1 ATR Cell Cycle Restart Plk1 controls recovery Plk-1 Chk Chk P Cell Cycle Arrest Wee1 caffeine
  8. 9. 9 1 1 ATR Claspin (1) Claspin Chk Chk P Cell Cycle Arrest
  9. 10. 9 1 1 ATR Cell Cycle Restart Plk1 controls checkpoint silencing Plk1 activation? Claspin Plk-1 Chk Chk P Cell Cycle Arrest Wee1
  10. 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
  11. 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
  12. 13. Conclusions <ul><li>Interdependent sequence of events </li></ul><ul><li>Commitment </li></ul><ul><li>Feed forward and Feedback </li></ul><ul><li>Bistability </li></ul><ul><li>Redundancy </li></ul>

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