1. Pph3 Dephosphorylation of Rad53 Is Required for Cell Recovery from MMS-Induced DNA Damage in Candida albicans
- Author
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Ada Hang-Heng Wong, Jianli Sang, Jiaxin Gao, Kun Chen, Kangdi Hu, Yue Wang, Wanjie Li, and Haitao Wang
- Subjects
lcsh:Medicine ,Cell Cycle Proteins ,Yeast and Fungal Models ,medicine.disease_cause ,chemistry.chemical_compound ,Gene Expression Regulation, Fungal ,Candida albicans ,Molecular Cell Biology ,Phosphoprotein Phosphatases ,Hydroxyurea ,Signaling in Cellular Processes ,Phosphorylation ,lcsh:Science ,DNA, Fungal ,Cellular Stress Responses ,Mutation ,Multidisciplinary ,biology ,Kinase ,Flow Cytometry ,Signaling Cascades ,Corpus albicans ,Medical Microbiology ,Phosphatase complex ,Research Article ,Signal Transduction ,DNA damage ,Genes, Fungal ,Protein Serine-Threonine Kinases ,Microbiology ,Stress Signaling Cascade ,Fungal Proteins ,Dephosphorylation ,Model Organisms ,Genetic Mutation ,Genetics ,medicine ,Biology ,Microbial Pathogens ,organic chemicals ,lcsh:R ,fungi ,Methyl Methanesulfonate ,biology.organism_classification ,Molecular biology ,Methyl methanesulfonate ,chemistry ,lcsh:Q ,Gene Function ,Gene Deletion ,Cytometry ,DNA Damage - Abstract
The pathogenic fungus Candida albicans switches from yeast growth to filamentous growth in response to genotoxic stresses, in which phosphoregulation of the checkpoint kinase Rad53 plays a crucial role. Here we report that the Pph3/Psy2 phosphatase complex, known to be involved in Rad53 dephosphorylation, is required for cellular responses to the DNA-damaging agent methyl methanesulfonate (MMS) but not the DNA replication inhibitor hydroxyurea (HU) in C. albicans. Deletion of either PPH3 or PSY2 resulted in enhanced filamentous growth during MMS treatment and continuous filamentous growth even after MMS removal. Moreover, during this growth, Rad53 remained hyperphosphorylated, MBF-regulated genes were downregulated, and hypha-specific genes were upregulated. We have also identified S461 and S545 on Rad53 as potential dephosphorylation sites of Pph3/Psy2 that are specifically involved in cellular responses to MMS. Therefore, our studies have identified a novel molecular mechanism mediating DNA damage response to MMS in C. albicans.
- Published
- 2012