Abstract

Protein phosphatase PP4 is composed of one catalytic subunit and one or two regulatory subunits and conserved in eukaryotic cells . The catalytic subunit CaPph3 forms a complex with the regulatory subunit CaPsy2, which dephosphorylates activated CaRad53 during adaptation to and recovery from MMS-mediated DNA damage. We show here that the N-terminal Y33A mutation of CaPsy2 blocks the interaction between CaPph3 and CaRad53, the deactivation of CaRad53 and the morphologic switch in recovery from genotoxic stress. In Saccharomyces cerevisiae , the ScPph3-ScPsy2-ScPsy4 complex functions to dephosphorylate γH2A. In this study, we show that CaPsy4 is a functional homolog of ScPsy4 and not involved in the deactivation of CaRad53 or CaHta, the ortholog of H2A. However, deletion of CaPSY4 causes C. albicans cells a sensitivity to genotoxic reagents and a defect in DNA damage-induced filamentation . CaPsy4 interacts with both CaPph3 and CaPsy2, but the function of CaPsy4 is independent of CaPph3 and CaPsy2 in response to genotoxic stress. C. albicans cells lacking CaPPH3 , CaPSY2 or CaPSY4 , and C. albicans cells carrying the Y33A mutation of CaPSY2 , show increased virulence to mice . Therefore, PP4 plays a negative role in regulating the DNA damage-induced filamentation and the virulence in C. albicans .