Modeling the Budding Yeast Cell Cycle

cln1∆ cln2∆ cln3∆ sic1∆

Simulation:

Change of parameters: ksn2'= ksn2"=0, Dn3=0, ksc1'=ksc1"=0.
Length of G1 phase: 5.8 min.
Mass at division: 5.8.

Experiments:

Schneider, B.L., Yang, Q.-H. and Futcher, A.B. (1996). Linkage of replication to Start by the Cdk inhibitor Sic1. Science 272:560-562.
[Abstract] [Article]
Tyers, M. (1996). The cyclin-dependent kinase inhibitor p40SIC1 imposes the requirement for Cln G1 cyclin function at Start. Proc. Natl. Acad. Sci. USA 93:7772-7776.
[Abstract] [Article]
Experimental results: Tyers: Fig. 2, viable with short G1 and very large cell size. Schneider: Fig. 3, viable.
Comments: In simulation, cell size is 2.2X WT. The short G1 phase of the quadruple mutant (and the sic1∆ mutant) indicates that Cdc6 (which is abundant in the G1 phase of these cells) is not a strong inhibitor of Clb5 kinase. The large size of the quaduple mutant indicates that Clb5-kinase cannot phosphorylate and inactivate Cdc6 efficiently.

In the absence of Sic1, although Clb5 kinase are able to initiate DNA synthesis early and to inactivate Cdh1, but to free Clb2 kinase from the inhibition by Cdc6, cells have to grow large enough to accumulate enough Clb5 to do the job. Only after Cdc6 is inhibited, can Clb2 kinase activity appear, and that triggers the positive feedback on its own synthesis and drives the cells into mitosis.