title: Pph3 dephosphorylation of Rad53 is required for cell recovery from MMS-induced DNA damage in Candida albicans.
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.
authors.affiliation: 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.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Gao
authors.forename: Wanjie
authors.initials: W
authors.lastname: Li
authors.forename: Ada Hang-Heng
authors.initials: AH
authors.lastname: Wong
authors.forename: Kangdi
authors.initials: K
authors.lastname: Hu
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianli
authors.initials: J
authors.lastname: Sang
mesh_terms: D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004249:DNA Damage; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006918:Hydroxyurea / Q000494:pharmacology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D008741:Methyl Methanesulfonate; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; D006918:Hydroxyurea