The Function of Fission Yeast Rho1-GEFs in the Control of Cell Growth and Division

Abstract

Guanine nucleotide exchange factors (GEFs) are directly responsible for the activation of Rho-family GTPases in response to physical and chemical stimuli and ultimately regulate numerous cellular responses such as polarized growth, morphogenesis, and movement. The GEF proteins are characterized by a Dbl-homology (DH) domain that contacts the Rho GTPases, to catalyzing nucleotide exchange, and an associated Pleckstrin homology (PH) domain, which fine-tunes the exchange process by a variety of mechanisms related to the binding of phosphoinositides. Most GEFs are divergent in regions outside the DH/ PH module and contain additional protein-protein or lipid-protein interaction domains that presumably dictate unique cellular functions. Fission yeast Rho1-GEFs act as a link between growth processes and the cell cycle machinery. In this chapter, we focus on the recent leaps in our understanding of how Rho1-GEFs control interphase and cytokinesis in fission yeast. Furthermore, we will go beyond mitosis and highlight the unexpected roles of Rho1-GEFs in the DNA damage response. in cell division. Double-mutant and phenotypic complementation results suggest that Rgf1p and Rgf3p are not functionally exchangeable. Disruption of rgf1 + in an rgf3 mutant ( ehs2-1 ) produced viable cells at 28°C but not at 37°C,