Molecular Mechanism of Cell Wall Integrity Checkpoint

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Cell wall remodeling and cell morphogenesis are tightly coordinated with progression of the cell cycle in many organisms. In the budding yeast, Saccharomyces cerevisiae, a major cell wall component, 1,3-β-glucan is synthesized at the budding site in the early stage of the cell cycle, and constructed in the primary septum before cytokinesis. Yeast possesses both forward and feedback system to achieve temporal and spatial regulation of cell wall construction, Forward system is composed of a cell cycle dependent morphological pathway that is regulated by small GTPase, Rholp. In addition, the feedback regulatory system, called cell wall integrity checkpoint was recently studied and characterized in our laboratory.We found that yeast cells stop growing at the specific stage of the cell cycle after perturbation of 1,3-β-glucan synthesis. These cells arrest with post-replicative DNA but quite low level of Clb2p, and without forming bipolar spindles. wacl (wall-checkpoint defective) mutation that abolishes this arrest causes the accumulation of C1b2p and CLB2 mRNA and leads to formation of bipolar spindles despite 1,3-β-glucan-synthesis perturbation. These results indicate the existence of a novel cell cycle checkpoint to coordinate entry into mitosis, and suggest that Waclp is required to achieve this checkpoint function through a transcriptional regulation of CLB2.