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Updated: May 17, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
Published on: September 6, 2024
Genetic interactions between protein phosphatases CaPtc2p and CaPph3p in response to genotoxins and rapamycin in
Jinrong Feng1, Yunying Zhao, Yinong Duan
1Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, China.
Abstract:
In Saccharomyces cerevisiae cells, both of the two PP2C protein phosphatases ScPtc2p and ScPtc3p and the PP4 protein phosphatase ScPph3 are responsible for ScRad53p dephosphorylation after the DNA methylation agent methylmethane sulfonate (MMS)-induced DNA damage. In this study, we show that CaPtc2p is not required for the CaRad53p dephosphorylation during the recovery from DNA damage, as is CaPph3p in Candida albicans. However, deletion of CaPPH3 has an additive effect on the sensitivity of C. albicans cells lacking CaPTC2 to MMS and the DNA synthesis inhibitor hydroxyurea (HU). In addition, deletion of CaPPH3 promotes in vitro filamentation of C. albicans cells. Furthermore, mutation of CaPTC2 is epistatic to that of CaPPH3 in the sensitivity of C. albicans cells to rapamycin. Therefore, CaPtc2p and CaPph3p might play a role in the target of rapamycin (TOR) signaling in C. albicans cells.
Insights
In Candida albicans, CaPtc2p and CaPph3p are not essential for DNA damage recovery. However, their combined absence increases sensitivity to DNA damaging agents and affects filamentation and rapamycin response.
Area of Science:
- Molecular Biology
- Mycology
- Cellular Biology
Background:
- Protein phosphatases play crucial roles in DNA damage response pathways.
- In Saccharomyces cerevisiae, ScPtc2p, ScPtc3p, and ScPph3 are involved in dephosphorylating ScRad53p after DNA damage.
- Understanding homologous protein functions in other fungi like Candida albicans is important for comparative genomics and cellular processes.
Purpose of the Study:
- To investigate the roles of CaPtc2p and CaPph3p in DNA damage response and other cellular processes in Candida albicans.
- To determine if CaPtc2p and CaPph3p are involved in CaRad53p dephosphorylation in C. albicans.
- To explore the potential involvement of these phosphatases in filamentation and target of rapamycin (TOR) signaling.
Main Methods:
- Gene deletion and mutant analysis in Candida albicans.
- Sensitivity assays using methylmethane sulfonate (MMS) and hydroxyurea (HU).
- In vitro filamentation assays and epistasis analysis for rapamycin sensitivity.
Main Results:
- CaPtc2p and CaPph3p are not required for CaRad53p dephosphorylation after DNA damage in C. albicans.
- Deletion of CaPPH3 exacerbates the MMS and HU sensitivity of CaPTC2 deletion mutants.
- CaPPH3 deletion promotes in vitro filamentation, and CaPTC2 mutation is epistatic to CaPPH3 mutation regarding rapamycin sensitivity.
Conclusions:
- CaPtc2p and CaPph3p have partially redundant roles in DNA damage tolerance in C. albicans.
- These phosphatases may contribute to regulating filamentation and TOR signaling pathways in this fungal species.
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