Béla Novák Molecular Network Dynamics Research Group Budapest University of Technology and Economics and Hungarian Academy of Sciences John J. Tyson Department.

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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 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 Modeling the yeast cell cycle

Low MPF High MPF balanced growth and division S M alternation of S and M checkpoint controls problems (S, M, growth)

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

mass/nucleus P Cdc2 Cdc13 Cdc2 Cdc13 Rum1 Ste9 Slp1 Wee1+Mik1 Cdc25 Time (min) SG2MG1S G2MG1S

mass/nucleus Cdc2:Cdc13 G1 S/G2 M

WT wee1  Balanced growth and division: size control WT

wee1  Balanced growth and division: size control

mass/nucleus Cdc2:Cdc13 G1 S/G2 M average

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

G1 S/G M metaphase checkpoint mass/nucleus Cdc2:Cdc13 G2/M Finish

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

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

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

G1 S/G2 M wee1  mass/nucleus Cdc2:Cdc13

wee1  mik1 - mass/nucleus Cdc2:Cdc13 G1 S/G2 M Mitotic catastrophe

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

Cdc2:Cdc13 G1 S/G2 M rum1  The Start module is not required during mitotic cycles

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

G1 S/G2 M rum1  wee1 ts 1 st 2 nd 3 rd 4 th mass/nucleus Cdc2:Cdc13 Cells become progressively smaller without size control

G1 S/G2 M cdc25  wee1 ts mass/nucleus Cdc2:Cdc13

cdc25  wee1 -

G1 S/G2 M In the absence of SK mass/nucleus Cdc2:Cdc13

Cdc20 S/G2 G1MM Cdc2 Cdc13 Cdh1 Cdc13 Rum1 S/G2G1 time (min) mass/DNA SK cdc13 Martin-Castellanos et al. (2000): Mol. Biol. Cell 11: X

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

John J. Tyson Attila Csikász-Nagy Kathy Chen John J. Tyson Attila Csikász-Nagy Kathy Chen Béla GyőrffyÁkos Sveiczer Béla GyőrffyÁkos Sveiczer John J. Tyson Attila Csikász-Nagy Kathy Chen John J. Tyson Attila Csikász-Nagy Kathy Chen Béla GyőrffyÁkos Sveiczer Béla GyőrffyÁkos Sveiczer

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