Genetic interaction between Ptc2 and protein phosphatase 4 (PP4) in the regulation of DNA damage response and virulence in Candida albicans

Abstract

ABSTRACTIn the pathogenic fungus Candida albicans, phosphoregulation of the checkpoint kinase Rad53 plays a crucial role in the filamentous growth response to genotoxic stresses. The protein phosphatase 4 (PP4) complex, containing Pph3 and either Psy2 or Psy4, is proved to play a critical role in Rad53 dephosphorylation. In previous studies, we characterized CaPtc2 (the ortholog of both Ptc2 and Ptc3 in Saccharomyces cerevisiae) as a potential DNA-damage-related protein phosphatase. In this study, we checked the genetic interaction of PTC2 with the PP4 complex in the DNA damage response pathway. The results suggest that Ptc2 shows a negative genetic interaction with Pph3, but positive genetic interaction with either Psy2 or Psy4 in response to genotoxic stress. Deletion of PTC2 alone resulted in no significant change in cell virulence, but double deletion of PTC2 PPH3 significantly decreased virulence, while double deletions of either PTC2 PSY2 or PTC2 PSY4 caused virulence levels similar to that shown by PSY2 or PSY4 single-gene deletion cells. Taken together, we propose that Ptc2 in C. albicans plays a compensatory role for Pph3 but is dependent on Psy2 and Psy4 in regulation of DNA damage and cell virulence.