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Cell cycle controls in fission yeast cells

Cell cycle controls in fission yeast cells. Attila Csikasz-Nagy Budapest University of Technology and Economics. Caltech, 27/03/2001. Cell cycle. Cytoplasmic cycle. Chromosomal cycle. chromosome segregation. misaligned chromosomes. APC. Cdk. +. Cdk. cyclin destruction. cyclin. Cdk.

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Cell cycle controls in fission yeast cells

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  1. Cell cycle controls in fission yeast cells Attila Csikasz-Nagy Budapest University of Technology and Economics Caltech, 27/03/2001

  2. Cell cycle Cytoplasmic cycle Chromosomal cycle

  3. chromosome segregation misaligned chromosomes APC Cdk + Cdk cyclin destruction cyclin

  4. Cdk cyclin APC & Cdk antagonism creates two cell cycle states S phase DNA replication + cell mass + degrades G2 & early mitosis G1 phase - - inactivates + APC + + + Chromosome segregation late mitosis

  5. ACT k3 Active Inactive APC APC k4 + + Cdk Cdk cyclin k2 Nucleus degraded cyclin Cdk k1 Cdk cyclin AA cyclin mass binding (fast)

  6. The phaseplane portrait G1 APC stable node saddle point S/M Stable node CDK nullcline: CDK APC nullcline:

  7. A B G1 APC APC mass = 1 ACT = 0 mass = 1.6 ACT = 0 Cell Growth S/M S/M CDK CDK D C G1 G1 APC APC mass = 1.75 ACT = 0.3 mass = 2 ACT = 1.5 Aligned chromosomes S/M CDK CDK

  8. Cdk cyclin CKI Cdk cyclin CKI CKI ACT k3 Active Inactive APC APC k4 + Cdk + k1 k2 mass degraded cyclin + k5 degraded CKI k6

  9. pre-Start post-Start S/G2/M CDK total nullcline S/G2/M CDK total CDK total Cell Growth CKI nullcline G1 CKI total CKI total

  10. Cdk cyclin Cdk cyclin ACT k3 Inactive Active APC APC k4 + + Cdk k1 k2 mass degraded cyclin + + kwee k25 kw k25 wee1 wee1 cdc25 cdc25 P kwr k25r P P

  11. M S/G2 M Cell Growth S/G2 M Cdk cyclin P G1 Cdk cyclin CDKT CDKA

  12. The negative feedback loop Nucleus Cdc20 ACT inactive unaligned chromosomes IE IE-P ACT active +APC Cdk Cdk cyclin Cdk mass cyclin AA

  13. APC P CKI Cdk Cdk cyclin cyclin wild type G1 S+G2+M G1 S+G2+M mass ACT M Cdk Wee1 Mik1 G2 cyclin G1 CKI APC cyclin

  14. APC P CKI Cdk Cdk cyclin cyclin wee1- G1 S+G2+M G1 S+G2+M mass ACT M Cdk G2 Mik1 cyclin G1 CKI APC

  15. P Cdk Cdk cyclin cyclin wee1- cdc25 mass ACT M ACT APC no positive feedback in G2 Cdk cyclin G1 CKI APC

  16. 350 350 300 300 250 250 Experimental data 200 200 150 150 100 100 Cycle time (min) Cycle time (min) 50 50 0 0 0 20 40 60 80 6 8 10 12 14 16 18 Cell number Birth size ( m m) 350 350 300 300 250 250 Simulationresults 200 200 150 150 100 100 Cycle time (min) Cycle time (min) 50 50 0 0 6 8 10 12 14 16 18 0 10 20 30 40 50 60 Birth size ( m m) Cell number

  17. cdc WT Wee1 activity (%) wee cut quantized Cdc25 activity (%) Robustness of the model wee1 P cdc2 cdc2 cdc13 cdc13 cdc25

  18. Budapest University of Technology and Economics Bela Novak Akos Sveiczer Bela Gyorffy Zsuzsa Pataki John Tyson Kathy Chen

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