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Updated: Jun 10, 2026
05:01
Assessment of DNA Double Strand Break Repair Activity Using High-throughput and Quantitative Luminescence-Based Reporter Assays
Published on: June 14, 2024
An Artemis polymorphic variant reduces Artemis activity and confers cellular radiosensitivity.
Lisa Woodbine1, Sofia Grigoriadou, Aaron A Goodarzi
1Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
DNA Repair
|August 3, 2010
Summary
A common Artemis gene variant impairs DNA repair, leading to radiosensitivity and immunodeficiency. This finding highlights how even partial Artemis dysfunction can cause significant health issues.
Area of Science:
- Genetics and Molecular Biology
- Immunology
- DNA Repair Mechanisms
Background:
- Artemis protein is crucial for V(D)J recombination and repairing DNA double-strand breaks (DSBs).
- Artemis deficiency causes radiosensitivity (RS) and severe combined immunodeficiency (SCID).
- Specific Artemis mutations lead to immunodeficiency and increased risk of EBV-associated lymphomas.
Purpose of the Study:
- To investigate the functional impact of a common polymorphic Artemis variant (c.512C > G: p.171P > R).
- To determine the clinical relevance of monoallelic expression of this Artemis variant.
Main Methods:
- In vitro assessment of Artemis endonuclease activity.
- Analysis of radiosensitivity and DSB repair in patient-derived cells.
- Complementation assays using Artemis cDNA expression.
Main Results:
- The c.512C > G variant reduced Artemis endonuclease activity by approximately 3-fold in vitro.
- Cells with monoallelic c.512C > G expression exhibited radiosensitivity and a G2 phase DSB repair defect.
- This variant had an additive negative effect on Artemis function when combined with another inactivating mutation.
Conclusions:
- Monoallelic expression of the c.512C > G Artemis variant impairs DNA repair, causing radiosensitivity and G2 phase DSB defects.
- The patient with this variant experienced adult-onset immunodeficiency, cancer, and myelodysplasia, suggesting broader clinical implications of reduced Artemis function.
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