Sds22 participates in Glc7 mediated Rad53 dephosphorylation in MMS-induced DNA damage in Candida albicans.
The protein kinase Rad53 and its orthologs play a fundamental role in regulating the DNA damage checkpoint in eukaryotes. Rad53 is activated by phosphorylation in response to DNA damage and deactivated by dephosphorylation after the damage is repaired. However, the phosphatases involved in Rad53 deactivation are not entirely understood. In this study, by investigating the consequences of overexpressing SDS22, a gene encoding a regulatory subunit of the PP1 phosphatase Glc7, in the human fungal pathogen Candida albicans, we discovered that Sds22 plays an important role in Rad53 dephosphorylation and thus the deactivation of the DNA damage checkpoint. Sds22 cellular levels increase when cells are exposed to DNA damaging agents and decrease after removing the genotoxins. Depletion of Glc7 has similar phenotypes. We provide evidence that Sds2 acts through inhibitory physical association with Glc7. Our findings provide novel insights into the mechanisms for the control of DNA damage checkpoint. Furthermore, SDS22 overexpression reduces C. albicans virulence in a mouse model of systemic infection, suggesting potential targets for developing antifungal drugs.
Key Laboratory of Cell Proliferation and Regulation, College of Life Sciences, Beijing Normal University, Beijing, China.
Guangyin
G
Yao
Key Laboratory of Cell Proliferation and Regulation, College of Life Sciences, Beijing Normal University, Beijing, China.
Junhua
J
Wan
Key Laboratory of Cell Proliferation and Regulation, College of Life Sciences, Beijing Normal University, Beijing, China.
Chunhua
C
Mu
Key Laboratory of Cell Proliferation and Regulation, College of Life Sciences, Beijing Normal University, Beijing, China.
Qizheng
Q
Liu
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore. Electronic address: mcbwangy@imcb.a-star.edu.sg.
Yue
Y
Wang
Key Laboratory of Cell Proliferation and Regulation, College of Life Sciences, Beijing Normal University, Beijing, China. Electronic address: jlsang@bnu.edu.cn.
Jianli
J
Sang
D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics*; D002176:Candida albicans / Q000235:genetics* / Q000472:pathogenicity; D002177:Candidiasis / Q000235:genetics* / Q000382:microbiology; D002467:Cell Nucleus / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D006801:Humans; D008741:Methyl Methanesulfonate / Q000633:toxicity; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; D005656:Fungal Proteins; D008741:Methyl Methanesulfonate; C000622710:Glc7 protein, C albicans; D017346:Protein Serine-Threonine Kinases; C000622708:Rad53 protein kinase, C elegans; C000622709:Sds22 protein, C albicans; D054645:Protein Phosphatase 1
Candida albicans; DNA damage checkpoint; Dephosphorylation; Phosphatases