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Understanding Yeast Cell Cycle Dynamics

This research explores modeling the yeast cell cycle to understand controls and problems in growth, division, and checkpoint mechanisms. Investigating the molecular network dynamics sheds light on size control and cell cycle progression.

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Understanding Yeast Cell Cycle Dynamics

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  1. Modeling the yeast cell cycle Béla Novák Molecular Network Dynamics Research Group Budapest University of Technology and Economics and Hungarian Academy of Sciences John J. Tyson Department of Biology Virginia Polytechnic Institute and State University

  2. S Low MPF alternation of S and M M High MPF balanced growth and division checkpoint controls problems (S, M, growth) Cell cycle engine

  3. Wee1 P M delay M S/G2 M Cdc25 Schizosaccharomyces pombe G1 mass/nucleus Cdc13 AA Cdc20 Cdc2 Finish Wee1 Cdc20 +APC P Cdc2 Cdc2 Cdc2 Cdc13 Cdc13 Cdc25 P Cdh1 G2/M Cdc2 Cdh1 Rum1 Cdc13 SK P Rum1 Rum1 AA Start

  4. 3.0 M 0.8 Cdc2:Cdc13 0.4 S/G2 G1 0 Hopf SN2 SN3 SN1 SNIC 0 1 2 3 4 5 mass/nucleus

  5. P Cdc2 Cdc13 Cdc2 Cdc13 0 50 100 150 200 250 300 S G2 M G1 S G2 M G1 S 5 mass/nucleus 4 3 2 1 0 Rum1 Ste9 Slp1 Wee1+Mik1 Cdc25 Time (min)

  6. 3.0 M 0.8 Cdc2:Cdc13 0.4 S/G2 G1 0 0 1 2 3 4 5 mass/nucleus

  7. Balanced growth and division: size control WT WT wee1 wee1

  8. Balanced growth and division: size control WT WT wee1 wee1

  9. 3.0 M 0.8 Cdc2:Cdc13 0.4 S/G2 G1 0 average 0 1 2 3 4 5 mass/nucleus

  10. normal division length normal birth length The cycle time in oversized cells

  11. G1 checkpoint M 0.4 Cdc2:Cdc13 S/G2 G1 0 0 2 3 5 1 4 mass/nucleus metaphase checkpoint G2 checkpoint 1.6 M M 1.2 0.4 Finish Cdc2:Cdc13 Cdc2:Cdc13 G2/M 0.8 S/G2 0.4 G1 G1 S/G2 0 0 4 4 0 2 3 5 0 2 3 5 1 1 mass/nucleus mass/nucleus Checkpoint controls

  12. Disruption of G2/M size control reveals a G1/S size control WT WT wee1 wee1

  13. delay Ste9 Schizosaccharomyces pombe mass/nucleus Cdc13 AA Slp1 Wee1 P Cdc2 Finish Wee1 Slp1 +APC P Cdc2 Cdc2 Cdc2 Cdc13 Cdc13 Cdc25 P Ste9 Cdc25 G2/M Cdc2 Rum1 Cdc13 SK P Rum1 Rum1 AA Start

  14. delay Cdc25 Schizosaccharomyces pombe unreplicated DNA mass/nucleus Cdc13 AA Cdc20 Mik1 P Cdc2 Finish Mik1 Cdc20 +APC P Cdc2 Cdc2 Cdc2 Cdc13 Cdc13 Cdc25 P Cdh1 G2/M Cdc2 Cdh1 Rum1 Cdc13 SK P Rum1 Rum1 AA Start

  15. 1.2 0.8 0.4 0 0 1 2 3 4 5 wee1 M Cdc2:Cdc13 S/G2 G1 mass/nucleus

  16. 1.2 0.8 0.4 0 0 1 2 3 4 5 Mitotic catastrophe wee1 mik1- M Cdc2:Cdc13 S/G2 G1 mass/nucleus

  17. Wee1 P delay Cdc25 Schizosaccharomyces pombe mass/nucleus Cdc13 AA Cdc20 Cdc2 Finish Wee1 Cdc20 +APC P Cdc2 Cdc2 Cdc2 Cdc13 Cdc13 Cdc25 P Cdh1 G2/M Cdc2 Cdh1 Rum1 Cdc13 SK P Rum1 Rum1 AA Start

  18. 3.0 0.8 0.4 0 0 1 2 3 4 5 The Start module is not required during mitotic cycles rum1 M Cdc2:Cdc13 S/G2 G1 mass/nucleus

  19. delay Schizosaccharomyces pombe mass/nucleus Cdc13 AA Cdc20 Wee1 P Cdc2 Finish Wee1 Cdc20 +APC P Cdc2 Cdc2 Cdc2 Cdc13 Cdc13 Cdc25 P Cdh1 Cdc25 G2/M Cdc2 Cdh1 Rum1 Cdc13 SK P Rum1 Rum1 AA Start

  20. 1st 2nd 3rd 4th Cells become progressively smaller without size control rum1 wee1ts 2.0 0.8 M Cdc2:Cdc13 0.4 S/G2 G1 0 0 1 2 3 4 5 mass/nucleus

  21. 0.8 0.4 0 0 1 2 3 4 5 cdc25 wee1ts M Cdc2:Cdc13 S/G2 G1 mass/nucleus

  22. cdc25 wee1-

  23. 3.0 0.8 0.4 0 In the absence of SK M Cdc2:Cdc13 S/G2 G1 0 1 2 3 4 5 6 mass/nucleus

  24. X Martin-Castellanos et al. (2000): Mol. Biol. Cell11: 543-554. Cdc20 Cdh1 Cdc2 Cdc13 Rum1 SK cdc13 mass/DNA Cdc13 M G1 S/G2 M G1 S/G2 time (min)

  25. Differential equations Analysis and computation Molecular network ??? Cell Physiology

  26. John J. Tyson Attila Csikász-Nagy Kathy Chen Béla Győrffy Ákos Sveiczer

  27. Hungarian Academy of Sciences Homepage: http://www.cellcycle.bme.hu/ Supporting agencies:

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