Table S1 a Dynamic Model of the Budding Yeast Cell Cycle

Table S1 A dynamic model of the budding yeast cell cycle

Table S1.A Equations for thedynamic model. Primed constants are evaluated in event function.

Algebraic Equation for Mass Balance / Module
/ S Phase Budding & S Phase DNA Synthesis
/ S Phase Budding & S Phase DNA Synthesis
/ G1 Phase & S Phase Budding & S Phase DNA Synthesis & G2-M Phase
/ S Phase Budding & S Phase DNA Synthesis
/ G1 Phase & S Phase Budding & G2-M Phase
/ G1 Phase & S Phase DNA Synthesis & G2-M Phase
/ G2-M Phase
/ S Phase DNA Synthesis & G2-M Phase
/ S Phase DNA Synthesis
/ S Phase DNA Synthesis
/ G2-M Phase
/ G2-M Phase
/ G1 Phase & G2-M Phase & M Phase Checkpoint
/ M Phase Checkpoint
/ M Phase Checkpoint
/ M Phase Checkpoint
/ M Phase Checkpoint
/ M Phase Checkpoint
/ All
/ S Phase Budding
/ S Phase DNA Synthesis
/ G1 Phase
/ G2-M Phase
/ S Phase Budding
/ G1 Phase
/ G2-M Phase
/ S Phase DNA Synthesis
/ M Phase Checkpoint
/ S Phase Budding
/ S Phase DNA Synthesis
/ G1 Phase
/ G2-M Phase
/ S Phase Budding
/ S Phase DNA Synthesis
/ G2-M Phase
/ G1 Phase
/ M Phase Checkpoint
/ G2-M Phase
Algebraic Equation for Binding / Module
/ S Phase Budding
/ S Phase Budding
/ S Phase Budding
/ S Phase Budding
/ S Phase DNA Synthesis
/ S Phase DNA Synthesis
/ S Phase DNA Synthesis
/ S Phase DNA Synthesis
/ G2-M Phase
/ G1 Phase
/ S Phase DNA Synthesis
/ S Phase Budding
/ G2-M Phase
/ G1 Phase
/ M Phase Checkpoint
/ M Phase Checkpoint
/ G2-M Phase
/ G1 Phase
/ G1 Phase
/ M Phase Checkpoint
/ S Phase Budding
/ S Phase DNA Synthesis
/ G1 Phase
/ G2-M Phase
/ S Phase DNA Synthesis
/ S Phase DNA Synthesis
/ G2-M Phase
/ G2-M Phase
/ M Phase Checkpoint
/ S Phase Budding
/ S Phase DNA Synthesis
/ G1 Phase
/ S Phase DNA Synthesis
/ G2-M Phase
/ G2-M Phase
/ G2-M Phase
/ M Phase Checkpoint
/ G2-M Phase
Differential Equation / Module
/ G2-M Phase
/ M Phase Checkpoint
/ S Phase Budding
/ S Phase DNA Synthesis
/ G2-M Phase
/ G1 Phase
/ S Phase DNA Synthesis
/ G2-M Phase
/ M Phase Checkpoint
/ S Phase Budding
/ S Phase DNA Synthesis
/ G2-M Phase
/ G1 Phase
/ G2-M Phase
/ G2-M Phase
/ S Phase DNA Synthesis
/ G2-M Phase
/ M Phase Checkpoint
/ M Phase Checkpoint
/ M Phase Checkpoint
/ S Phase Budding
/ S Phase DNA Synthesis
/ G1 Phase
/ G2-M Phase
/ S Phase Budding
/ G1 Phase
/ G2-M Phase
/ S Phase DNA Synthesis
/ M Phase Checkpoint
/ S Phase Budding
/ S Phase DNA Synthesis
/ G1 Phase
/ G2-M Phase
/ G2-M Phase
/ S Phase Budding
/ S Phase DNA Synthesis
/ G2-M Phase
/ S Phase Budding
/ S Phase Budding
/ S Phase Budding

Table S1.B A list of biochemical components

Component / Definition / Module / Initial Concentration
Cln3 / G1 cyclin (G1/S phase transition control) / S Phase Budding / 3.00×10-7 [M]
Bck2 / Back-up / S Phase Budding / 2.00×10-7 [M]
Cln2 / G1 cyclin (G1/S phase transition control) / S Phase Budding / 3.30×10-9 [M]
Clb5 / B-type cyclin / S Phase DNA Synthesis / 1.26×10-9 [M]
Clb2 / B-type cyclin / G2-M Phase / 3.67×10-8 [M]
Sic1 / CDK inhibitor / G1 Phase / 2.89×10-7 [M]
Hct1 / Controller for spindle formation checkpoint / G2-M Phase / 7.30×10-9 [M]
Cdc20 / Activator for APC/C / G2-M Phase / 4.46×10-7 [M]
Cdc6 / Regulator for starting S phase / S Phase DNA Synthesis / 1.99×10-7 [M]
Origin / Replication origin / S Phase DNA Synthesis / 9.57×10-11 [M]
Pds1 / Cerculin / G2-M Phase / 1.71×10-9 [M]
Esp1 / Separin / G2-M Phase / 1.71×10-9 [M]
Cdc14 / Enzyme for dephosphorylation (M phase exit) / M Phase Checkpoint / 5.53×10-9 [M]
Net1 / Controller for M phase checkpoint (M phase exit) / M Phase Checkpoint / 6.24×10-8 [M]
Cdc15 / Ser/Thr kinase (M phase exit) / M Phase Checkpoint / 6.68×10-7 [M]
Tem1 / Controller for M phase checkpoint (M phase exit) / M Phase Checkpoint / 6.16×10-11 [M]
Bub2 / Controller for M phase checkpoint (M phase exit) / M Phase Checkpoint / 1.99×10-7 [M]
Lte1 / Controller for M phase checkpoint (M phase exit) / M Phase Checkpoint / 3.00×10-7 [M]
SCF / Complex for identifying ubiquitin / All / 4.66×10-9 [M]
SBF / Cln2 transcription factor / S Phase Budding / 2.07×10-9 [M]
MBF / Clb5 transcription factor / S Phase DNA Synthesis / 2.00×10-9 [M]
Swi5 / Sic1 transcription factor / G1 Phase / 9.79×10-9 [M]
Mcm1 / Clb2 transcription factor / G2-M Phase / 2.97×10-9 [M]
Cln2-P / Phosphorylated Cln2 / S Phase Budding / 2.63×10-10 [M]
Sic1-P / Phosphorylated Sic1 / G1 Phase / 5.47×10-11 [M]
Hct1-P / Phosphorylated Hct1 / G2-M Phase / 1.62×10-11 [M]
Cdc6-P / Phosphorylated Cdc6 / S Phase DNA Synthesis / 8.08×10-16 [M]
Tem1-P / Phosphorylated Tem1 / M Phase Checkpoint / 6.10×10-10 [M]
SBF-P / Phosphorylated SBF / S Phase Budding / 0 [M]
MBF-P / Phosphorylated MBF / S Phase DNA Synthesis / 0 [M]
Swi5-P / Phosphorylated Swi5 / G1 Phase / 3.42×10-11 [M]
Mcm1-P / Phosphorylated Mcm1 / G2-M Phase / 7.96×10-9 [M]
SCB / SWI4/SWI6 cell cycle box / S Phase Budding / 2.00×10-9 [M]
MCB / MluI cell cycle box / S Phase DNA Synthesis / 2.00×10-9 [M]
Enhancer(Clb2) / Clb2 gene enhancer / G2-M Phase / 1.93×10-9 [M]
Enhancer(Sic1) / Sic1 gene enhancer / G1 Phase / 1.82×10-9 [M]
Enhancer(Cdc15) / Cdc15 gene enhancer / M Phase Checkpoint / 1.89×10-9 [M]
Pds1-P / Phosphorylated Pds1 / G2-M Phase / 7.03×10-11 [M]
SBF-P:SCB / Complex of SBF-P and SCB / S Phase Budding / 0 [M]
MBF-P:MCB / Complex of MBF-P and MCB / S Phase DNA Synthesis / 0 [M]
Swi5:Enhancer(Sic1) / Swi5-bound Enhancer(Sic1) / G1 Phase / 1.78×10-10 [M]
Mcm1-P:Enhancer(Clb2) / Phosphorylated Mcm1-bound Enhancer(Clb2) / G2-M Phase / 6.91×10-11 [M]
Sic1:Clb5 / Complex of Sic1 and Clb5 / S Phase DNA Synthesis / 3.63×10-8 [M]
Sic1:Clb2 / Complex of Sic1 and Clb2 / G2-M Phase / 1.06×10-11 [M]
Cdc6:Origin / Cdc6-bound Origin / S Phase DNA Synthesis / 1.90×10-9 [M]
Pds1:Esp1 / Complex of Pds1 and Esp1 / G2-M Phase / 2.92×10-10 [M]
Cdc14:Net1 / Complex of Cdc14 and Net1 / M Phase Checkpoint / 3.45×10-8 [M]
Cln3:SBF:P / Complex of Cln3, SBF and P / S Phase Budding / 3.10×10-14 [M]
Bck2:SBF:P / Complex of Bck2, SBF and P / S Phase Budding / 2.07×10-14 [M]
Cln2:SBF:P / Complex of Cln2, SBF and P / S Phase Budding / 6.83×10-17 [M]
Clb5:SBF:P / Complex of Clb5, SBF and P / S Phase Budding / 2.60×10-17 [M]
Cln3:MBF:P / Complex of Cln3, MBF and P / S Phase DNA Synthesis / 3.00×10-14 [M]
Bck2:MBF:P / Complex of Bck2, MBF and P / S Phase DNA Synthesis / 2.00×10-14 [M]
Cln2:MBF:P / Complex of Cln2, MBF and P / S Phase DNA Synthesis / 6.61×10-17 [M]
Clb5:MBF:P / Complex of Clb5, MBF and P / S Phase DNA Synthesis / 2.51×10-17 [M]
Cln2:Hct1:P / Complex of Cln2, Hct1 and P / G2-M Phase / 2.41×10-15 [M]
Cln2:Sic1:P / Complex of Cln2, Sic1 and P / G1 Phase / 9.55×10-13 [M]
Clb5:Cdc6:P / Complex of Clb5, Cdc6 and P / S Phase DNA Synthesis / 2.50×10-13 [M]
Clb2:Cln2:P / Complex of Clb2, Cln2 and P / S Phase Budding / 1.21×10-13 [M]
Clb2:Mcm1:P / Complex of Clb2, Mcm1 and P / G2-M Phase / 1.09×10-15 [M]
Clb2:Swi5:P / Complex of Clb2, Swi5 and P / G1 Phase / 3.60×10-15 [M]
Lte1:Tem1:P / Complex of Lte1, Tem1 and P / M Phase Checkpoint / 9.23×10-16 [M]
Cdc15:Net1:P / Complex of Cdc15, Net1 and P / M Phase Checkpoint / 4.17×10-11 [M]
Cdc14:Hct1-P / Complex of Cdc14 and Hct1-P / G2-M Phase / 8.97×10-13 [M]
Cdc14:Swi5-P / Complex of Cdc14 and Swi5-P / G1 Phase / 1.89×10-12 [M]
Cdc14:Sic1-P / Complex of Cdc14 and Sic1-P / G1 Phase / 3.02×10-12 [M]
Bub2:Tem1-P / Complex of Bub2 and Tem1-P / M Phase Checkpoint / 1.21×10-9 [M]
SCF:Cln2-P / Complex of SCF and Cln2-P / S Phase Budding / 1.22×10-11 [M]
SCF:Cdc6-P / Complex of SCF and Cdc6-P / S Phase DNA Synthesis / 3.76×10-15 [M]
SCF:Sic1-P / Complex of SCF and Sic1-P / G1 Phase / 2.55×10-12 [M]
Cdc20:Clb5 / Complex of Cdc20 and Clb5 / S Phase DNA Synthesis / 5.61×10-10 [M]
Hct1:Clb2 / Complex of Hct1 and Clb2 / G2-M Phase / 2.68×10-9 [M]
Tem1-P:Enhancer(Cdc15) / Phosphorylated Tem1-bound Enhancer(Cdc15) / M Phase Checkpoint / 1.15×10-10 [M]
Cdc20:Pds1:P / Complex of Cdc20, Pds1 and P / G2-M Phase / 7.64×10-13 [M]
Hct1:Pds1:P / Complex of Hct1, Pds1 and P / G2-M Phase / 1.25×10-14 [M]
SCF:Pds1-P / Complex of SCF and Pds1-P / G2-M Phase / 3.27×10-10 [M]
Cdc20-P / Phosphorylated Cdc20 / G2-M Phase / 4.33×10-13 [M]
Net1-P / Phosphorylated Net1 / M Phase Checkpoint / 1.04×10-7 [M]
mRNA(Cln2) / Cln2 mRNA / S Phase Budding / 1.01×10-18 [M]
mRNA(Clb5) / Clb5 mRNA / S Phase DNA Synthesis / 5.52×10-19 [M]
mRNA(Clb2) / Clb2 mRNA / G2-M Phase / 1.61×10-9 [M]
mRNA(Sic1) / Sic1 mRNA / G1 Phase / 3.47×10-9 [M]
mRNA(Cdc6) / Cdc6 mRNA / S Phase DNA Synthesis / 2.25×10-9 [M]
mRNA(Pds1) / Pds1 mRNA / G2-M Phase / 1.61×10-9 [M]
mRNA(Cdc15) / Cdc15 mRNA / M Phase Checkpoint / 2.28×10-9 [M]
TCln2 / Total Cln2 / S Phase Budding / 3.30×10-9 [M]
TClb5 / Total Clb5 / S Phase DNA Synthesis / 3.81×10-8 [M]
TClb2 / Total Clb2 / G2-M Phase / 3.92×10-8 [M]
TSic1 / Total Sic1 / G1 Phase / 3.26×10-7 [M]
THct1 / Total Hct1 / G2-M Phase / 9.98×10-9 [M]
TCdc20 / Total Cdc20 / G2-M Phase / 4.47×10-7 [M]
TCdc6 / Total Cdc6 / S Phase DNA Synthesis / 2.01×10-7 [M]
TPds1 / Total Pds1 / G2-M Phase / 2.00×10-9 [M]
TNet1 / Total Net1 / M Phase Checkpoint / 9.69×10-8 [M]
TCdc15 / Total Cdc15 / M Phase Checkpoint / 6.69×10-7 [M]
TTem1 / Total Tem1 / M Phase Checkpoint / 6.15×10-11 [M]
TSBF / Total SBF / S Phase Budding / 2.07×10-9 [M]
TMBF / Total MBF / S Phase DNA Synthesis / 2.00×10-9 [M]
TSwi5 / Total Swi5 / G1 Phase / 9.96×10-9 [M]
TMcm1 / Total Mcm1 / G2-M Phase / 2.98×10-9 [M]
TCln2-P / Total Cln2-P / S Phase Budding / 2.73×10-10 [M]
TSic1-P / Total Sic1-P / G1 Phase / 6.04×10-11 [M]
THct1-P / Total Hct1-P / G2-M Phase / 1.72×10-11 [M]
TCdc6-P / Total Cdc6-P / S Phase DNA Synthesis / 4.57×10-15 [M]
TTem1-P / Total Tem1-P / M Phase Checkpoint / 1.94×10-9 [M]
TSBF-P / Total SBF-P / S Phase Budding / 0 [M]
TMBF-P / Total MBF-P / S Phase DNA Synthesis / 0 [M]
TSwi5-P / Total Swi5-P / G1 Phase / 3.59×10-11 [M]
TMcm1-P / Total Mcm1-P / G2-M Phase / 8.02×10-9 [M]
TPds1-P / Total Pds1-P / G2-M Phase / 3.97×10-10 [M]
Mass / Auxiliary variable / S Phase Budding / 5.50×10-7[-]
DNA_con / Auxiliary variable / S Phase DNA Synthesis / 1.00×10-8 [-]
Spindle_con / Auxiliary variable / G2-M Phase / 0 [-]
Budding_con / Auxiliary variable / S Phase Budding / 1.00×10-8[-]
Cln3_act / Auxiliary variable / S Phase Budding / 1.00×10-8[M]
Bck2_act / Auxiliary variable / S Phase Budding / 2.48×10-13[M]
DNA_replication / Auxiliary variable / S Phase DNA Synthesis / 0 [-]
Spindle / Auxiliary variable / G2-M Phase / 0 [-]
Chromatin_separation / Auxiliary variable / G2-M Phase / 0 [-]
M_phase_exit / Auxiliary variable / M Phase Checkpoint / 0 [-]
P / Phosphate / All / 1.00×10-6 [M] (constant)
Gene(Cln2) / Cln2 gene / S Phase Budding / 1.00×10-9 [M] (constant)
Gene(Clb5) / Clb5 gene / S Phase DNA Synthesis / 1.00×10-9 [M] (constant)
Gene(Clb2) / Clb2 gene / G2-M Phase / 1.00×10-9 [M] (constant)
Gene(Sic1) / Sic1 gene / G1 Phase / 1.00×10-9 [M] (constant)
Gene(Cdc6) / Cdc6 gene / S Phase DNA Synthesis / 1.00×10-9 [M] (constant)
Gene(Pds1) / Pds1 gene / G2-M Phase / 1.00×10-9 [M] (constant)
Gene(Cdc15) / Cdc15 gene / M Phase Checkpoint / 1.00×10-9 [M] (constant)
TCln3 / Total Cln3 / S Phase Budding / 3.00×10-7 [M] (constant)
TBck2 / Total Bck2 / S Phase Budding / 2.00×10-7 [M] (constant)
TOrigin / Total Origin / S Phase DNA Synthesis / 2.00×10-9 [M] (constant)
TEsp1 / Total Esp1 / G2-M Phase / 2.00×10-9 [M] (constant)
TCdc14 / Total Cdc14 / M Phase Checkpoint / 4.00×10-8 [M] (constant)
TBub2 / Total Bub2 / M Phase Checkpoint / 2.00×10-7 [M] (constant)
TLte1 / Total Lte1 / M Phase Checkpoint / 3.00×10-7 [M] (constant)
TSCF / Total SCF / All / 5.00×10-9 [M] (constant)
TSCB / Total SCB / S Phase Budding / 2.00×10-9 [M] (constant)
TMCB / Total MCB / All / 2.00×10-9 [M] (constant)
TEnhancer(Clb2) / Total Clb2 enhancer / G2-M Phase / 2.00×10-9 [M] (constant)
TEnhancer(Sic1) / Total Sic1 enhancer / G1 Phase / 2.00×10-9 [M] (constant)
TEnhancer(Cdc15) / Total Cdc15 enhancer / M Phase Checkpoint / 2.00×10-9 [M] (constant)
Cellsize / Auxiliary constant for cell size / S Phase Budding / 1.00×10-7 [-] (constant)

Table S1.C A list of biochemical parameters

Parameter / Definition / Module / Default Value
Kb1 / Binding constant between SBF, P and Cln3 / S Phase Budding / 5×107 [M-2]
Kb2 / Binding constant between SBF, P and Bck2 / S Phase Budding / 5×107 [M-2]
Kb3 / Binding constant between SBF, P and Cln2 / S Phase Budding / 1×107 [M-2]
Kb4 / Binding constant between SBF, P and Clb5 / S Phase Budding / 1×107 [M-2]
Kb5 / Binding constant between MBF, P and Cln3 / S Phase DNA Synthesis / 5×107 [M-2]
Kb6 / Binding constant between MBF, P and Bck2 / S Phase DNA Synthesis / 5×107 [M-2]
Kb7 / Binding constant between MBF, P and Cln2 / S Phase DNA Synthesis / 1×107 [M-2]
Kb8 / Binding constant between MBF, P and Clb5 / S Phase DNA Synthesis / 1×107 [M-2]
Kb9 / Binding constant between Hct1, P and Cln2 / G2-M Phase / 1×108 [M-2]
Kb10 / Binding constant between Sic1, P and Cln2 / G1 Phase / 1×109 [M-2]
Kb11 / Binding constant between Cdc6, P and Clb5 / S Phase DNA Synthesis / 1×109 [M-2]
Kb12 / Binding constant between Cln2, P and Clb2 / S Phase Budding / 1×109 [M-2]
Kb13 / Binding constant between Mcm1, P and Clb2 / G2-M Phase / 1×107 [M-2]
Kb14 / Binding constant between Swi5, P andClb2 / G1 Phase / 1×107 [M-2]
Kb15 / Binding constant between Tem1, P and Lte1 / M Phase Checkpoint / 5×107 [M-2]
Kb16 / Binding constant between Net1, P and Cdc15 / M Phase Checkpoint / 1×109 [M-2]
Kb17 / Binding constant between Hct1-P and Cdc14 / G2-M Phase / 1×107 [M-1]
Kb18 / Binding constant between Swi5-P andCdc14 / G1 Phase / 1×107 [M-1]
Kb19 / Binding constant between Sic1-P and Cdc14 / G1 Phase / 1×107 [M-1]
Kb20 / Binding constant between Tem1-P and Bub2 / M Phase Checkpoint / 1×107 [M-1]
Kb21 / Binding constant between SBF-P and SCB / S Phase Budding / 9×107 [M-1]
Kb22 / Binding constant between MBF-P and MCB / S Phase DNA Synthesis / 5×107 [M-1]
Kb23 / Binding constant between Swi5 and Enhancer(Sic1) / G1 Phase / 1×107 [M-1]
Kb24 / Binding constant between Mcm1-P and Enhancer(Clb2) / G2-M Phase / 4.5×106 [M-1]
Kb25 / Binding constant between Cdc6 and Origin / S Phase DNA Synthesis / 1×108 [M-1]
Kb26 / Binding constant between Sic1 and Clb5 / S Phase DNA Synthesis / 1×108 [M-1]
Kb27 / Binding constant between Sic1 and Clb2 / G2-M Phase / 1×103 [M-1]
Kb28 / Binding constant between Pds1 and Esp1 / G2-M Phase / 1×108 [M-1]
Kb29 / Binding constant between Cdc14 and Net1 / M Phase Checkpoint / 1×108 [M-1]
Kb30 / Binding constant between Cln2-P and SCF / S Phase Budding / 1×107 [M-1]
Kb31 / Binding constant between Cdc6-P and SCF / S Phase DNA Synthesis / 1×109 [M-1]
Kb32 / Binding constant between Sic1-P and SCF / G1 Phase / 1×107 [M-1]
Kb33 / Binding constant between Clb5 and Cdc20_ / S Phase DNA Synthesis / 1×106 [M-1]
Kb34 / Binding constant between Pds1, P and Cdc20 / G2-M Phase / 1×109 [M-2]
Kb35 / Binding constant between Pds1, P and Hct1 / G2-M Phase / 1×109 [M-2]
Kb36 / Binding constant between Clb2 and Hct1 / G2-M Phase / 1×107 [M-1]
Kb37 / Binding constant between Tem1-P and Enhancer(Cdc15) / M Phase Checkpoint / 1×108 [M-1]
Kb38 / Binding constant between Pds1-P and SCF / G2-M Phase / 1×109 [M-1]
kx1 / Reaction rate constant forCln3:SBF:P / S Phase Budding / 4×104 [min-1]
kx2 / Reaction rate constant for Bck2:SBF:P / S Phase Budding / 4×104 [min-1]
kx3 / Reaction rate constant for Cln2:SBF:P / S Phase Budding / 1×103 [min-1]
kx4 / Reaction rate constant for Clb5:SBF:P / S Phase Budding / 1×103[min-1]
kx5 / Reaction rate constant for Cln3:MBF:P / S Phase DNA Synthesis / 4×104 [min-1]
kx6 / Reaction rate constant for Bck2:MBF:P / S Phase DNA Synthesis / 4×104 [min-1]
kx7 / Reaction rate constant for Cln2:MBF:P / S Phase DNA Synthesis / 1×103 [min-1]
kx8 / Reaction rate constant for Clb5:MBF:P / S Phase DNA Synthesis / 1×103 [min-1]
kx9 / Reaction rate constant for Cln2:Hct1:P / G2-M Phase / 2×104 [min-1]
kx10 / Reaction rate constant for Cln2:Sic1:P / G1 Phase / 7×103 [min-1]
kx11 / Reaction rate constant for Clb5:Cdc6:P / S Phase DNA Synthesis / 8×104 [min-1]
kx12 / Reaction rate constant for Clb2:Cln2:P / S Phase Budding / 1×104 [min-1]
kx13 / Reaction rate constant for Clb2:Mcm1:P / G2-M Phase / 6×106 [min-1]
kx14 / Reaction rate constant for Clb2:Swi5:P / G1 Phase / 5×104 [min-1]
kx15 / Reaction rate constant for Cdc20 and P / G2-M Phase / 5 [M-1 min-1]
kx16 / Reaction rate constant for Lte1:Tem1:P / M Phase Checkpoint / 8×103 [min-1]
kx17 / Reaction rate constant for Cdc15:Net1:P / M Phase Checkpoint / 1×105 [min-1]
kx18 / Reaction rate constant for SBF-P / S Phase Budding / 5 [min-1]
kx19 / Reaction rate constant for MBF-P / S Phase DNA Synthesis / 5 [min-1]
kx20 / Reaction rate constant for Cln2-P / S Phase Budding / 5 [min-1]
kx21 / Reaction rate constant for Cdc6-P / S Phase DNA Synthesis / 5 [min-1]
kx22 / Reaction rate constant for Mcm1-P / G2-M Phase / 0.1 [min-1]
kx23 / Reaction rate constant for Cdc20-P / G2-M Phase / 5 [min-1]
kx24 / Reaction rate constant for Cdc14:Hct1-P / G2-M Phase / 50 [min-1]
kx25 / Reaction rate constant for Cdc14:Swi5-P / G1 Phase / 150 [min-1]
kx26 / Reaction rate constant for Cdc14:Sic1-P / G1 Phase / 100 [min-1]
kx27 / Reaction rate constant for Bub2:Tem1-P / M Phase Checkpoint / 20 [min-1]
kx28 / Reaction rate constant for Net1-P / M Phase Checkpoint / 40 [min-1]
kx29 / Reaction rate constant for SCF:Cln2-P / S Phase Budding / 5 [min-1]
kx30 / Reaction rate constant for SCF:Cdc6-P / S Phase DNA Synthesis / 100 [min-1]
kx31 / Reaction rate constant for SCF:Sic1-P / G1 Phase / 2.50×103 [min-1]
kx32 / Reaction rate constant for Cdc20:Clb5 / S Phase DNA Synthesis / 1 [min-1]
kx33 / Reaction rate constant for Cdc20:Pds1:P / G2-M Phase / 3×104 [min-1]
kx34 / Reaction rate constant for Hct1:Pds1:P / G2-M Phase / 8×105 [min-1]
kx35 / Reaction rate constant for Hct1:Clb2 / M Phase Checkpoint / 20 [min-1]
kx36 / Reaction rate constant for Pds1-P / G2-M Phase / 3 [min-1]
kx37 / Reaction rate constant for SCF:Pds1-P / G2-M Phase / 100 [min-1]
kx38 / Reaction rate constant for Cellsize / S Phase Budding / 0.03125 [-]
kx39 / Reaction rate constant for Clb2 / G2-M Phase / 0.03 [M-1]
kx40 / Reaction rate constant for TCln2 / S Phase Budding / 0.3 [M-1]
kx41 / Reaction rate constant for Spindle_con / G2-M Phase / 5 [M min-1]
kp1 / Translation rate constant for mRNA(Cln2) / S Phase Budding / 20 [min-1]
kp2 / Translation rate constant formRNA(Clb5) / S Phase DNA Synthesis / 20 [min-1]
kp3 / Translation rate constant formRNA(Cdc6) / S Phase DNA Synthesis / 20 [min-1]
kp4 / Translation rate constant for mRNA(Sic1) / G1 Phase / 20 [min-1]
kp5 / Translation rate constant for mRNA(Clb2) / G2-M Phase / 20 [min-1]
kp6 / Translation rate constant for mRNA(Pds1) / G2-M Phase / 20 [min-1]
kp7 / Translation rate constant for mRNA(Cdc15) / M Phase Checkpoint / 20 [min-1]
kpd1 / Decomposition rate constant for Cln2 / S Phase Budding / 0.03 [min-1]
kpd2 / Decomposition rate constant for Clb5 / S Phase DNA Synthesis / 0.03 [min-1]
kpd3 / Decomposition rate constant for Clb2 / G2-M Phase / 0.03 [min-1]
kpd4 / Decomposition rate constant for Sic1 / G1 Phase / 0.08 [min-1]
kpd5 / Decomposition rate constant for Cdc6 / S Phase DNA Synthesis / 0.03 [min-1]
kpd6 / Decomposition rate constant for Cdc15 / M Phase Checkpoint / 0.03 [min-1]
kpd7 / Decomposition rate constant for Swi5 / G1 Phase / 0.009 [min-1]
kpd8 / Decomposition rate constant for Cln2-P / S Phase Budding / 0.03 [min-1]
kpd9 / Decomposition rate constant for Sic1-P / G1 Phase / 0.03 [min-1]
kpd10 / Decomposition rate constant for Cdc6-P / S Phase DNA Synthesis / 0.03 [min-1]
kpd11 / Decomposition rate constant for Sic1:Clb5 / S Phase DNA Synthesis / 0.03 [min-1]
kpd12 / Decomposition rate constant for Sic1:Clb2 / G2-M Phase / 0.03 [min-1]
kpd13 / Decomposition rate constant for Cdc6:Origin / S Phase DNA Synthesis / 0.03 [min-1]
kpd14 / Decomposition rate constant for Cln2:Sic1:P / G1 Phase / 0.03 [min-1]
kpd15 / Decomposition rate constant for Clb5:Cdc6:P / S Phase DNA Synthesis / 0.03 [min-1]
kpd16 / Decomposition rate constant for Clb2:Cln2:P / S Phase Budding / 0.03 [min-1]
kpd17 / Decomposition rate constant for Clb2:Mcm1:P / G2-M Phase / 0.03 [min-1]
kpd18 / Decomposition rate constant for Clb2:Swi5:P / G1 Phase / 0.05 [min-1]
kpd19 / Decomposition rate constant for Cdc20:Clb5 / S Phase DNA Synthesis / 0.03 [min-1]
kpd20 / Decomposition rate constant for Hct1:Clb2 / G2-M Phase / 0.03 [min-1]
kpd21 / Decomposition rate constant for Cdc20 / G2-M Phase / 0.03 [min-1]
kpd22 / Decomposition rate constant for Cdc20-P / G2-M Phase / 0.03 [min-1]
kpd23 / Decomposition rate constant for SCF:Cln2-P / S Phase Budding / 0.03 [min-1]
kpd24 / Decomposition rate constant for SCF:Sic1-P / G1 Phase / 0.03 [min-1]
kpd25 / Decomposition rate constant for SCF:Cdc6-P / S Phase DNA Synthesis / 0.03 [min-1]
kpd26 / Decomposition rate constant for Cdc14:Sic1-P / G1 Phase / 0.03 [min-1]
km1 / Transcription rate constant forGene(Cln2) and SBF-P:SCB / S Phase Budding / 20 [min-1]
km2 / Transcription rate constant for Gene(Clb5) and MBF-P:MCB / S Phase DNA Synthesis / 20 [min-1]
km3 / Transcription rate constant for Gene(Cdc6) and Swi5:Enhancer(Sic1) / S Phase DNA Synthesis / 13 [min-1]
km4 / Transcription rate constant for Gene(Cdc6) and SBF-P:SCB / S Phase DNA Synthesis / 20 [min-1]
km5 / Transcription rate constant for Gene(Sic1) and Swi5:Enhancer(Sic1) / G1 Phase / 20 [min-1]
km6 / Transcription rate constant for Gene(Clb2) and Mcm1-P:Enhancer(Clb2) / G2-M Phase / 20 [min-1]
km7 / Transcription rate constant for Gene(Pds1) and Mcm1-P:Enhancer(Clb2) / G2-M Phase / 20 [min-1]
km8 / Transcription rate constant for Gene(Cdc15) and Tem1-P:Enhancer(Cdc15) / M Phase Checkpoint / 20 [min-1]
kmd1 / Decomposition rate constant for mRNA(Cln2) / S Phase Budding / 0.5 [min-1]
kmd2 / Decomposition rate constant for mRNA(Clb5) / S Phase DNA Synthesis / 0.5 [min-1]
kmd3 / Decomposition rate constant for mRNA(Clb2) / G2-M Phase / 0.5 [min-1]
kmd4 / Decomposition rate constant for mRNA(Sic1) / G1 Phase / 0.5 [min-1]
kmd5 / Decomposition rate constant for mRNA(Cdc6) / S Phase DNA Synthesis / 0.5 [min-1]
kmd6 / Decomposition rate constant for mRNA(Pds1) / G2-M Phase / 0.5 [min-1]
kmd7 / Decomposition rate constant for mRNA(Cdc15) / M Phase Checkpoint / 0.5 [min-1]
kother1 / Threshold of Spindle_con for TCdc20 synthesis / G2-M Phase / 7.48×10-6 [-]
kother2 / Threshold of Mass for entering S phase / S Phase Budding / 7×10-7[-]
Ke1 / Constant for event / All / 1.1×10-5 [M]
Ke2 / Constant for event / All / 1.9×10-5 [M]
Ke3 / Constant for event / All / 10-7 [M]
Ke4 / Constant for event / All / 10-10 [M]
Ke5 / Constant for event / All / 2×10-7 [-]
Ke6 / Constant for event / All / 5×10-10 [M]
Ke7 / Constant for event / All / 1.5×10-9 [M]
Ke8 / Constant for event / All / 9×10-7 [M]
Ke9 / Constant for event / All / 7×10-7 [-]

Table S1.D Event function. The following expressions are evaluated in every step of numerical integration of differential-algebraic equations. The variables with subscript “initial” indicate initial values for the corresponding variables.“” indicates the floor function.

Table S2 Search parameters in optimization of each module by GAs

Module 1(G1phase)

Parameter / Lower / Upper
Kb10 / 3×107 / 2×109
Kb14 / 1×106 / 1×109
Kb23 / 3×106 / 1×108
kx10 / 1×102 / 1×105
kx14 / 3×103 / 3×105

Module 2(S phase budding)

Parameter / Lower / Upper
Kb1 / 1×106 / 1×109
Kb2 / 1×106 / 1×109
Kb12 / 1×108 / 1×1010
Kb21 / 1×107 / 1×109
Kb30 / 1×106 / 1×108
kx12 / 1×103 / 1×105
kx18 / 1×10-1 / 1×102
kx20 / 1×10-1 / 1×102
kx29 / 1×10-1 / 1×102

Module 3(S phase DNA synthesis)

Parameter / Lower / Upper
Kb5 / 1×106 / 1×109
Kb6 / 1×106 / 1×109
Kb11 / 1×107 / 1×1010
Kb22 / 1×107 / 5×108
kx19 / 1×100 / 3×101
kx30 / 1×101 / 1×103

Module 4(G2-M phase)

Parameter / Lower / Upper
Kb9 / 1×106 / 1×109
Kb13 / 1×106 / 1×109
Kb24 / 1×106 / 5×107
Kb28 / 1×106 / 1×109
Kb34 / 1×106 / 1×109
kx9 / 1×103 / 1×106
kx22 / 1×10-2 / 1×101
kx33 / 1×104 / 1×105
kx37 / 3×101 / 5×102

Module 5(M phase checkpoint)

Parameter / Lower / Upper
Kb16 / 1×106 / 1×109
Kb17 / 1×106 / 1×109
Kb29 / 1×106 / 1×109
Kb36 / 1×106 / 1×109
kx35 / 5×100 / 1×102

Table S3 If-then rules for scoring a simulated model

The simulated model is scored under two types of conditions: the normalconditions and the strict conditions. A normal score is added if the simulation result satisfies the normal conditions. A high score is added if the simulated result satisfies the strict conditions i.e., reproduces the intrinsic behaviors for the cell cycle,otherwise, a score is subtracted. The score is not subtracted even if the result does not satisfy the normal conditions, while the score is subtracted if the result does not satisfy the strict conditions. The fitness function is calculated for two cycles. Here, the scoring rules are shown for the first cycle.In scoring the second cycle, the elapsed time for the first cycle is subtracted from t, and then the same scoring rules as the first cycle are adapted to the second cycle.

Table S3.AThe scoring rule for wild type.

The dynamic feature of each component is described as follows: The Cln2 level increases just before S phase and disappears after S phase. The Clb5 level increases just after the beginning of S phase, and then disappears at the middle of M phase. The Clb2 level increasesjust before M phase, and disappears at the end of M phase. Sic1 is expressed during G1 phase and at the anaphase of M. Cln3 is active from the end of G1 phase to the middle of S phase. Origin replication is activefrom S phase to the end of the cycle. Spindle formation is active during M phase.

Component / Normal condition / Strict condition
Cln2 / /
Clb5 / /
Clb2 / /
Sic1 /

Cln3 activity /
Origin replication /
Spindle formation /

Table S3.B The scoring rule for Sic1 knockout mutant.

The duration of G1 phase is shorten by 30 % or 10 min and the changes in all components are 10 min advanced.

Component / Normal condition / Strict condition
Cln2 / /
Clb5 / /
Clb2 / /
Cln3 activity /
Origin replication /
Spindle formation /

Table S3.C The scoring rule for Cln2 knockout mutant.