STUDYING THE CELL CYCLE AND PHEROMONE RESPONSE PATHWAY INTERACTION IN YEAST Saccharomycfes cerevisiae

ALICIA GRANDE; ALTSZYLER E; BALENZUELA P; BRUNO L; LAJE R; ARIEL CHERNOMORETZ; ALEJANDRO COLMAN LERNER

Potrero de Funes

Congreso; SAIB 47th Annual Meeting Argentine Society of Biochemistry and Molecular Biology XLVII Reunión Anual Argentina de Investigación en Bioquímica y Biología Molecular; 2011

Society of Biochemistry and Molecular Biology XLVII Reunión Anual Argentina de Investigación en Bioquímica y Biología Molecular

In haploid yeast, mating pheromone triggers a fate decision: arrest of the cell cycle in G1 and initiation of mating events. To do that, the MAP kinase of the pheromone response pathway (PRP) Fus3 activates the cyclin dependent kinase inhibitor Far1, which binds to and inhibits all three G1 cyclins complexes, Cdc28/Clns. Cdc28/Cln2 activity is essential to pass the START G1 checkpoint, while Cdc28/Cln3 is required earlier in G1 to drive the expression of Cln2. This has two important consequences: a) inhibition of Cdc28/Clns causes cells to arrest in G1, and b) since Cdc28/Cln2 can block pheromone response, its inhibition by Far1 acts as a positive feedback loop. Because the signaling pathway is physically supported by a network of interacting proteins, evolving in space and time according to fundamental laws of reaction, diffusion and transport, here we propose a basic mathematical model, with a small number of parameters and dynamical variables, that reproduces the observed biological phenomena: the interaction between the cell cycle and the PRP. As a first approximation, we used a set of nonlinear ordinary differential equations (ODE) that describe the dynamics of the simultaneously occurring reactions. We tested our model using fluorescent microscopy, measuring fluorescent proteins used as reporters of the PRP and morphology for the cell cycle.