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Pph3 Dephosphorylation of Rad53 is Required for Cell Recovery from MMS-induced DNA Damage in Candida Albicans

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Journal PLoS One
Date 2012 May 19
PMID 22606354
Citations 11
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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.

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References
1.
Keogh M, Kim J, Downey M, Fillingham J, Chowdhury D, Harrison J . A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature. 2005; 439(7075):497-501. DOI: 10.1038/nature04384. View

2.
Heideker J, Lis E, Romesberg F . Phosphatases, DNA damage checkpoints and checkpoint deactivation. Cell Cycle. 2007; 6(24):3058-64. DOI: 10.4161/cc.6.24.5100. View

3.
Atir-Lande A, Gildor T, Kornitzer D . Role for the SCFCDC4 ubiquitin ligase in Candida albicans morphogenesis. Mol Biol Cell. 2005; 16(6):2772-85. PMC: 1142423. DOI: 10.1091/mbc.e05-01-0079. View

4.
Ahn J, Li X, Davis H, Canman C . Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain. J Biol Chem. 2002; 277(22):19389-95. DOI: 10.1074/jbc.M200822200. View

5.
Carty M, McGrath S, Dixon K . UV light-induced DNA synthesis arrest in HeLa cells is associated with changes in phosphorylation of human single-stranded DNA-binding protein. EMBO J. 1994; 13(9):2114-23. PMC: 395063. DOI: 10.1002/j.1460-2075.1994.tb06487.x. View