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Updated: Jun 15, 2026

Fission Yeast as a Platform for Antibacterial Drug Screens Targeting Bacterial Cytoskeleton Proteins
Published on: April 26, 2024
A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor
Yoko Yashiroda1, Reika Okamoto, Kaori Hatsugai
1Chemical Genomics Research Group/Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan. ytyy@riken.jp
Abstract:
The telomere-associated protein tankyrase 1 is a poly(ADP-ribose) polymerase and is considered to be a promising target for cancer therapy, especially for BRCA-associated cancers. However, an efficient assay system for inhibitor screening has not been established, mainly due to the difficulty of efficient preparation of the enzyme and its substrate. Here, we report a cell-based assay system for detecting inhibitory activity against tankyrase 1. We found that overexpression of the human tankyrase 1 gene causes a growth defect in the fission yeast Schizosaccharomyces pombe. Chemicals that restore the growth defect phenotype can be identified as potential tankyrase 1 inhibitors. We performed a high-throughput screen using this system, and identified flavone as a compound that restores the growth of yeast cells overexpressing tankyrase 1. Indeed, flavone inhibited poly(ADP-ribosyl)ation of proteins caused by overexpression of tankyrase 1 in yeast cells. This system allows rapid identification of inhibitory activity against tankyrase 1 and is amenable to high-throughput screening using robotics.
Insights
Researchers developed a novel yeast-based assay to screen for tankyrase 1 inhibitors, crucial for cancer therapy. This system successfully identified flavone as a potential inhibitor, paving the way for new drug discovery.
Area of Science:
- Biochemistry
- Molecular Biology
- Yeast Genetics
Background:
- Tankyrase 1, a poly(ADP-ribose) polymerase, is a key target in cancer therapy, particularly for BRCA-associated cancers.
- Developing efficient screening systems for tankyrase 1 inhibitors is challenging due to difficulties in enzyme and substrate preparation.
Purpose of the Study:
- To establish a robust cell-based assay system for detecting inhibitory activity against tankyrase 1.
- To facilitate high-throughput screening for potential tankyrase 1 inhibitors.
Main Methods:
- Utilized the fission yeast Schizosaccharomyces pombe as a model system.
- Developed a growth restoration assay where compounds counteracting tankyrase 1 overexpression-induced growth defects were identified.
- Performed high-throughput screening using robotics.
Main Results:
- Overexpression of human tankyrase 1 gene induced a growth defect in Schizosaccharomyces pombe.
- Identified flavone as a compound that restored yeast cell growth.
- Confirmed that flavone inhibits poly(ADP-ribosyl)ation mediated by tankyrase 1 in yeast cells.
Conclusions:
- The developed yeast-based system provides an efficient method for identifying tankyrase 1 inhibitory activity.
- This assay is amenable to high-throughput screening, accelerating the discovery of novel tankyrase 1 inhibitors for cancer therapy.
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