Related Experiment Video
Updated: Mar 19, 2026
Genetic Studies of Human DNA Repair Proteins Using Yeast as a Model System
Published on: March 18, 2010
Sds22 participates in Glc7 mediated Rad53 dephosphorylation in MMS-induced DNA damage in Candida albicans
Guangyin Yao1, Junhua Wan1, Chunhua Mu1
1Key Laboratory of Cell Proliferation and Regulation, College of Life Sciences, Beijing Normal University, Beijing, China.
Abstract:
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.
Insights
The study reveals that Sds22 regulates the DNA damage checkpoint in Candida albicans by dephosphorylating Rad53. Overexpressing SDS22 also reduces fungal virulence, suggesting new antifungal drug targets.
Area of Science:
- Molecular Biology
- Cellular Biology
- Mycology
Background:
- The protein kinase Rad53 is crucial for eukaryotic DNA damage checkpoints.
- Rad53 activation and deactivation involve phosphorylation and dephosphorylation, respectively.
- The phosphatases mediating Rad53 deactivation remain incompletely characterized.
Purpose of the Study:
- To investigate the role of SDS22, a regulatory subunit of protein phosphatase 1 (PP1) Glc7, in DNA damage checkpoint control in Candida albicans.
- To elucidate the mechanism by which Sds22 influences Rad53 dephosphorylation.
- To assess the impact of SDS22 modulation on C. albicans virulence.
Main Methods:
- Overexpression of SDS22 in Candida albicans.
- Analysis of Rad53 phosphorylation status under various conditions.
- Investigation of Sds22-Glc7 physical interactions.
- Assessment of C. albicans virulence in a mouse model.
Main Results:
- SDS22 overexpression promotes Rad53 dephosphorylation and DNA damage checkpoint deactivation.
- Sds22 levels fluctuate in response to DNA damaging agents.
- Glc7 depletion phenocopies SDS22 overexpression effects.
- Sds22 inhibits Glc7 activity through physical association.
- SDS22 overexpression attenuates C. albicans virulence.
Conclusions:
- Sds22 is a key regulator of Rad53 dephosphorylation and DNA damage checkpoint control in C. albicans.
- Sds22 functions by inhibiting the phosphatase Glc7.
- Modulating Sds22 activity offers a potential strategy for developing novel antifungal therapies targeting virulence.
Related Concept Videos
02:36DNA Damage can Stall the Cell Cycle
02:36DNA Damage Can Stall the Cell Cycle