Simulations of mitotic progression of cells containing <i>cdc15-2</i>, <i>NET1-6cdk</i>, <i>tem1-3, cdc28-as1</i>, and <i>GAL-CLB2dbΔ cdc5-as1</i> mutations.

<p>(<b>A</b>) In MEN mutants such as <i>cdc15-2</i>, Cdc14 is transiently released and resequestered. Cdc20 block-and-release was presimulated with inactive Cdc15 (<i>effc15</i> = 0). (<b>B</b>) In <i>tem1-3</i> temperature sensitive mutant (MEN inactive), Cdc14 is transiently released and cells are arrested in telophase. Simulation was started at metaphase by Cdc20 deprivation (<i>k</i>_s,20 = 0) for 15 min with total concentration of Tem1, initial conditions of Tem1 and MEN were set to zero. Cdc20 was activated at time zero (<i>k</i>_s,20 = 0.015) (<b>C</b>) In <i>NET1-6cdk</i> cells ME occurs with a delay, as typical of FEAR mutants. Cdc20 block-and-release was presimulated with no Net1 phosphorylation by Cdk/Clb2 (<i>k</i>_k,12 = <i>k</i>_k,34 = 0). (<b>D</b>) Double MEN and FEAR mutations, such as <i>NET1-6cdk cdc15-2</i>, do not show transient release of Cdc14 and arrest in telophase. Cdc20 block-and-release was presimulated with inactive Cdc15 (<i>effc15</i> = 0) and no Net1 phosphorylation by Cdk/Clb2 (<i>k</i>_k,12 = <i>k</i>_k,34 = 0). (<b>E</b>) When Cdk kinase activity is inhibited, there is no Cdc14 release. Both Cdk/Clb2 and Cdc5 phosphorylation on Net1 are diminished in <i>cdc28-as1</i> mutant. Simulation was done similar to wild-type cells except that INH was set to 5 to inhibit Cdk kinase activity. (<b>F</b>) Our model predicts that when Cdc5 is inhibited, overexpressed Clb2 cannot induce Cdc14 release with or without active Cdc20. Simulation was started at metaphase by Cdc20 deprivation, overexpression of Clb2 and inactive Cdc5 for 15 min (<i>k</i>_s,20 = 0, <i>k</i>_s,b2 = 0.6, <i>k</i>_d,b2 = <i>k</i>_d,b2′ = effpol = 0). Cdc20 was added back at time zero (<i>k</i>_s,20 = 0.015).