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

2. Cytoplasmic cycleChromosomal cycle Cell cycle

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

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

5. binding (fast) AA Nucleus + degraded cyclin ACT Inactive Active Cdk cyclin Cdk + APC Cdk cyclin Cdk k1k1 k2k2 k4k4 k3k3 mass

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

7. CDK APC mass = 1 ACT = 0 mass = 2 ACT = 1.5 mass = 1.75 ACT = 0.3 mass = 1.6 ACT = 0 G1 S/M G1 S/M AB CD Cell Growth Aligned chromosomes

8. CKI degraded cyclin + Cdk cyclin Cdk CKI Cdk cyclin k1k1 k2k2 Inactive Active APC k4k4 k3k3 k5k5 k6k6 ACT CKI degraded CKI mass + +

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

10. P degraded cyclin Cdk cyclin Cdk Inactive Active APC + Cdk cyclin P P k4k4 k3k3 k1k1 k2k2 k 25 k 25r kwkw k wr k wee k 25 ++ + ACT mass cdc25 wee1 cdc25

11. CDK A CDK T Cdk cyclin Cdk cyclin P M Cell Growth S/G2 G1 S/G2 M M

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

13. Cdk cyclin CKI APC Wee1 Mik1 wild type ACT mass G1S+G2+M G1S+G2+M APC CKI Cdk cyclin P Cdk cyclin G1 G2 M

14. Cdk cyclin CKI APC Mik1 wee1 - ACT APC CKI mass Cdk cyclin P Cdk cyclin G1S+G2+M G1S+G2+M G1 G2 M

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

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

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