Related Experiment Video
Updated: May 23, 2026
06:24
Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
Published on: February 13, 2019
Particulate Hexavalent Chromium Inhibits RAD51 Paralogs Necessary for RAD51 Filament Formation and Stabilization
Aggie R Williams1, Idoia Meaza1, Haiyan Lu1
1Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
Occupational Health
|May 22, 2026
Summary
Hexavalent chromium (Cr(VI)) exposure represses RAD51 paralogs, crucial for DNA repair. Cr(VI) impairs homologous recombination repair by targeting RAD51D early, hindering DNA repair and potentially causing lung cancer.
Area of Science:
- Molecular Biology
- Environmental Health
- Genetics
Background:
- Hexavalent chromium (Cr(VI)) is a known lung carcinogen.
- Cr(VI) induces DNA double-strand breaks and chromosome instability.
- Cr(VI) impairs homologous recombination repair by targeting RAD51.
Purpose of the Study:
- To investigate the effects of Cr(VI) exposure on RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3).
- To understand the role of RAD51 paralogs in Cr(VI)-induced DNA damage and repair inhibition.
Main Methods:
- Exposure of WTHBF-6 human lung cells to zinc chromate.
- RNA sequencing, RT-qPCR, Western blotting, and immunofluorescence assays.
- Proximity Ligation Assay (PLA) to assess protein-protein interactions.
Main Results:
- Cr(VI) exposure transcriptionally repressed all RAD51 paralogs.
- Cr(VI) inhibited RAD51D foci formation after acute and prolonged exposure.
- Cr(VI) inhibited XRCC2 and XRCC3 foci formation after prolonged exposure.
- Cr(VI) reduced RAD51D protein levels and its interaction with RAD51.
Conclusions:
- Cr(VI) inhibits all RAD51 paralogs, suggesting a broad impact on homologous recombination repair.
- RAD51D may be an early target of Cr(VI), leading to impaired RAD51 filament formation and function.
- Cr(VI) significantly disrupts DNA repair mechanisms, contributing to its carcinogenic potential.
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