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Updated: Jun 1, 2026
08:35
Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
The dominant negative mutant Artemis enhances tumor cell radiosensitivity
Hai Liu1, XiaoNan Sun, Shuo Zhang
1Cancer Institute, Zhejiang University School of Medicine, The Second Affiliated Hospital, Hangzhou, China.
Summary
A mutant Artemis fragment enhances tumor cell radiosensitivity by inhibiting DNA repair. This dominant-negative fragment targets Artemis activity, offering a novel strategy for improving radiotherapy outcomes in cervical cancer.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Tumor radioresistance is a major cause of radiotherapy failure.
- Targeting DNA double-strand break repair is a key strategy to enhance radiosensitivity.
- Artemis plays a crucial role in DNA repair and cell radiosensitivity.
Purpose of the Study:
- To investigate the effect of a mutant Artemis fragment on the radiosensitivity of human cervical cancer cells.
- To explore the underlying molecular mechanisms of mutant Artemis-mediated radiosensitization.
Main Methods:
- Constructed eukaryotic expression vectors for full-length and mutant Artemis fragments.
- Utilized HeLa cells for stable transfection and radiosensitivity assays (clonogenic assay).
- Monitored DNA repair dynamics (γH2AX foci assay) and protein interactions (co-immunoprecipitation, Western blot).
Main Results:
- Expression of the mutant Artemis fragment (D37N-413aa) delayed DNA double-strand break (DSB) rejoining after irradiation.
- This delay in DNA repair significantly enhanced the radiosensitivity of HeLa cells.
- The mutant Artemis fragment was found to bind DNA-PKcs and ATM, inhibiting the phosphorylation of endogenous Artemis.
Conclusions:
- A dominant-negative mutant Artemis fragment enhances tumor cell radiosensitivity by blocking endogenous Artemis activity and DNA repair.
- This study demonstrates a novel mechanism for modulating radiosensitivity by targeting Artemis.
- Artemis represents a promising therapeutic target for improving cancer radiotherapy.
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