rad-50 Antibody

Introduction to RAD50 Protein and RAD50 Antibody

The RAD50 protein is a critical component of the MRN complex (MRE11-RAD50-NBS1), which coordinates DNA double-strand break (DSB) repair, telomere maintenance, and DNA damage signaling . Structurally, RAD50 belongs to the structural maintenance of chromosomes (SMC) family, featuring ATPase domains and a zinc-hook motif that facilitates DNA end bridging . RAD50 antibodies, such as the monoclonal Rad50 antibody [13B3] (GTX70228), are essential tools for detecting RAD50 expression and studying its functional roles in genomic stability and disease .

Development and Validation of RAD50 Antibody

The Rad50 antibody [13B3] (GeneTex, GTX70228) is a mouse-derived monoclonal IgG1 antibody validated for specificity and performance across multiple applications:

This antibody detects RAD50 in nuclear compartments, as demonstrated in HeLa cells, and cross-reacts with rodent and primate homologs .

Role in DNA Damage Response and Cancer Therapy

• Cisplatin Sensitivity: RAD50 silencing enhances cisplatin cytotoxicity in breast cancer cells by impairing DSB repair, leading to increased DNA damage accumulation .

• Ovarian Cancer: RAD50 overexpression activates NF-κB via CARD9 interaction, promoting tumor aggressiveness and epithelial-mesenchymal transition (EMT) .

• Therapeutic Targeting: Dominant-negative RAD50 mutants sensitize cisplatin-resistant tumors to therapy, inducing telomere shortening and apoptosis .

Mechanistic Insights

• DNA Demethylation: RAD50 collaborates with Tet1 to facilitate active DNA demethylation during somatic cell reprogramming, enhancing induced pluripotent stem cell (iPSC) generation .

• Immune Signaling: Cytosolic RAD50 binds dsDNA and recruits CARD9 to activate NF-κB, linking DNA damage sensing to IL-1β production in innate immunity .

Clinical Implications and Therapeutic Potential

• Biomarker Potential: Reduced RAD50 expression correlates with high-grade breast tumors and poor prognosis .

• Chemosensitization: Combining RAD50-targeted inhibitors (e.g., adenoviral mutants) with cisplatin synergistically enhances tumor regression in xenograft models .

• Germ Cell Development: RAD50 deficiency disrupts meiosis, causing infertility in mice due to defective DSB repair and SSC loss .

Emerging Insights and Future Directions

Recent studies highlight RAD50’s dual roles in DNA repair and immune regulation, positioning it as a multifunctional target for cancer and autoimmune therapies. Ongoing research focuses on:

• Small-Molecule Inhibitors: Targeting RAD50’s ATPase domain to disrupt MRN complex activity .

• Combination Therapies: Pairing RAD50 modulation with PARP inhibitors or immune checkpoint blockers .