Characterize compounds that affect V(D)J recombination and chromsomal translocation using MP-HTGTS

V(D)J recombination represents a vital mechanism responsible for generating antibodies and T-cell receptors (TCR). This intricate process encompasses various stages, such as chromatin looping, RAG1/2 incision, end processing, and ligation. In our study, we conducted extensive screening using a diverse array of drugs from the FDA-approved list. Our primary objective was to gain insights into the impact of these drugs on V(D)J recombination and to elucidate potential side effects associated with their use. Notably, among the drugs examined, HDAC inhibitors stood out as they appeared to modulate V(D)J recombination initiation by potentially regulating upstream events. This investigation contributes valuable information to our understanding of how pharmaceutical agents may influence the intricate process of V(D)J recombination and highlights the distinctive role played by HDAC inhibitors in this context. Overall design: Various murine proB cells including WT and Ku70-/- were arrested by STI-571 to induce V(D)J recombination, the V-J recombination in IgK locus were systematically captured using all four JK1 coding end as bait by HTGTS.