Modeling the Budding Yeast Cell Cycle

Problems with the model


Observed Phenotype

Simulated Phenotype



Viable, grows slowly with reduced size at birth and reduced size at budding
(Jorgensen et al., 2002;
Wasch & Cross, 2002).

Viable, normal growth rate, small at birth, normal size at budding.

Cdh1 promotes proteolysis of some activator of START.

cdh1∆ cdc6∆2-49

Viable, large size with an extended G2 phase
(Calzada et al., 2001).

Viable, size between WT and cdh1∆ with a slightly shorter G2.


CLB1 clb2∆

(Richardson et al., 1992).

Inviable, sister chromatid separation occurs 1.5 min after nuclear division.

Parameter settings may be faulty or model criteria for cell viability may be too strict.

CLB1 clb2∆ cdh1∆

Inviable in glucose, viable in galactose
(Cross, 2003).

Viable in both glucose and galactose.

Clb1 may not be a perfect backup of Clb2, which may be essential for activation of APC/Cdc20.

GAL-CLB2 sic1∆

Inviable, telophase arrest
(Toyn et al., 1997).

Inviable, division occurs in an unbudded cell.

A delay in the onset of mitosis by the morphogenesis checkpoint may cause telophase arrest.

sic1∆ cdh1∆

Most cells are able to exit from mitosis after the 1st cycle and arrest in the 2nd cycle as large budded cells with replicated DNA
(Schwab et al., 1997;
Visintin et al., 1997;
Wasch & Cross, 2002;
Archambault et al., 2003).

Completes 1st cycle, but no bud in the 2nd cycle.
If budding problem is ignored, then the mutant would be viable.

See discussion of the triple-antagonist strain.

sic1∆ cdc6∆2-49 cdh1∆


Inviable, arrests as a "4-cell body" objects with 2 short spindles and 4C DNA content
(Archambault et al., 2003).

The triple-antagonist strain has additional cytokinesis defect than the double mutant sic1∆ cdh1∆.

Inviable, telophase arrest with 2C DNA content.

Cdc14 may trigger mitotic exit in the presence of high Clb2 kinase activity. See mutant simulation for details.


swi5∆ cdh1∆

Inviable, similar to triple-antagonist
(Archambault et al., 2003).

Inviable, similar to triple-antagonist.

Same as triple-antagonist.


(Yamamoto et al., 1996).

Inviable, Esp1 active before chromosome alignment.

The model neglects the role of Cdc5 in activating the Scc1 as the substrate for Esp1.

CLB1 clb2∆ pds1∆

(Shirayama et al., 1999).

Inviable for the wrong reasons. If both single mutants are viable then the double mutant would be viable as well.

Does Clb2 have a new role in inactivating Esp1?

bub2∆ in nocodazole

Exits from mitosis after many hours in nocodazole
(Hoyt et al., 1991;
Alexandru et al., 1999).

Tightly arrests in metaphase in nocodazole.

May be a new cross talk from the BUB2 pathway to the MAD2 pathway.