title: Protein phosphatase Pph3 and its regulatory subunit Psy2 regulate Rad53 dephosphorylation and cell morphogenesis during recovery from DNA damage in Candida albicans.
abstract: The ability of the pathogenic fungus Candida albicans to switch cellular morphologies is important for infection and virulence. Recent studies have revealed that C. albicans yeast cells can switch to filamentous growth under genotoxic stress in a manner dependent on the DNA replication/damage checkpoint. Here, we have investigated the functions of Pph3 (orf19.4378) and Psy2 (orf19.3685), whose orthologues in Saccharomyces cerevisiae mediate the dephosphorylation of the DNA damage checkpoint kinase Rad53 and the histone variant H2AX during recovery from DNA damage. Deleting PPH3 or PSY2 causes hypersensitivity to DNA-damaging agents, including cisplatin, methylmethane sulfonate (MMS), and UV light. In addition, pph3Δ and psy2Δ cells exhibit strong filamentous growth under genotoxic stress. Flow cytometry analysis shows that the mutant cells have lost the ability to adapt to genotoxic stress and remain arrested even after the stress is withdrawn. Furthermore, we show that Pph3 and Psy2 are required for the dephosphorylation of Rad53, but not H2AX, during DNA damage recovery. Taken together, these results show that C. albicans Pph3 and Psy2 have important roles in mediating genotoxin-induced filamentous growth and regulating Rad53 dephosphorylation.
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, People's Republic of China.
authors: Ling Ling
authors: LL
authors: Sun
authors: Wan Jie
authors: WJ
authors: Li
authors: Hai Tao
authors: HT
authors: Wang
authors: Jie
authors: J
authors: Chen
authors: Ping
authors: P
authors: Deng
authors: Yue
authors: Y
authors: Wang
authors: Jian Li
authors: JL
authors: Sang
mesh_terms: D000595:Amino Acid Sequence; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D016415:Sequence Alignment; D013312:Stress, Physiological; D014466:Ultraviolet Rays
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D008741:Methyl Methanesulfonate; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; D002945:Cisplatin