ArticleJournal of gastroenterology and hepatology research2017
Impact of RAD51C-mediated Homologous Recombination on Genomic Integrity in Barrett's Adenocarcinoma Cells.
Article in Journal of gastroenterology and hepatology research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Elevated APE1 Dysregulates Homologous Recombination and Cell Cycle Driving Genomic Evolution, Tumorigenesis, and Chemoresistance in Esophageal Adenocarcinoma.Gastroenterology · 2023Article
- RAD51 Is Implicated in DNA Damage, Chemoresistance and Immune Dysregulation in Solid Tumors.Cancers · 2022Article
- DNA repair pathways as a novel therapeutic strategy in esophageal cancer: A review study.Cancer reports (Hoboken, N.J.) · 2022Review
- Integrated genomics and comprehensive validation reveal drivers of genomic evolution in esophageal adenocarcinoma.Communications biology · 2021Article
- Single-Strand Annealing in Cancer.International journal of molecular sciences · 2021Review
- RAD51 Inhibitor Reverses Etoposide-Induced Genomic Toxicity and Instability in Esophageal Adenocarcinoma Cells.Archives of clinical toxicology · 2020Article
- Role of apurinic/apyrimidinic nucleases in the regulation of homologous recombination in myeloma: mechanisms and translational significance.Blood cancer journal · 2018Article
- Rad51 and Systemic Inflammatory Indicators as Novel Prognostic Markers in Esophageal Squamous Cell Carcinoma.Technology in cancer research & treatmentArticle
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIn normal cells, RAD51-mediated homologous recombination (HR) is a precise DNA repair mechanism which plays a key role in the maintenance of genomic integrity and stability. However, elevated (dysregulated) RAD51 is implicated in genomic instability and is a potential target for treatment of certain cancers, including Barrett's adenocarcinoma (BAC). In this study, we investigated genomic impact and translational significance of moderate vs. strong suppression of RAD51 in BAC cells.
methodsBAC cells (FLO-1 and OE33) were transduced with non-targeting control (CS) or RAD51-specific shRNAs, mediating a moderate (40-50%) suppression or strong (80-near 100%) suppression of the gene. DNA breaks, spontaneous or following exposure to DNA damaging agent, were examined by comet assay and 53BP1 staining. Gene expression was monitored by microarrays (Affymetrix). Homologous recombination (HR) and single strand annealing (SSA) activities were measured using plasmid based assays.
resultsWe show that although moderate suppression consistenly inhibits/reduces HR activity, the strong suppression is associated with increase in HR activity (by ~15 - ≥ 50% in various experiments), suggesting activation of RAD51-independent pathway. Contrary to moderate suppression, a strong suppression of RAD51 is associated with a significant induced DNA breaks as well as altered expression of genes involved in detection/processing of DNA breaks and apoptosis. Stronger RAD51 suppression was also associated with mutagenic single strand annealing mediated HR. Suppression of RAD51C inhibited RAD51-independent (SSA-mediated) HR in BAC cells.
conclusionElevated (dysregulated) RAD51 in BAC is implicated in both the repair of DNA breaks as well as ongoing genomic rearrangements. Moderate suppression of this gene reduces HR activity, whereas strong or near complete suppression of this gene activates RAD51C-dependent HR involving a mechanism known as single strand annealing (SSA). SSA-mediated HR, which is a mutagenic HR pathway, further disrupts genomic integrity by increasing DNA breaks in BAC cells.
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