The DTX3L Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated through targeted disruption of the DTX3L gene. This product provides a loss-of-function model for investigating DTX3L-dependent processes without selection of a monoclonal clone, preserving genetic heterogeneity typical of polyclonal cells. The polyclonal format is suitable for pooled functional genomics studies and large-scale screening applications where clonal variation is not required.
The host cell line, 786-O, is a tumorigenic human renal epithelial cell line originally established from a primary clear cell renal adenocarcinoma. It is characterized by a well-documented VHL mutation, a hallmark of clear cell renal cell carcinoma (ccRCC), making it a widely accepted model for studying ccRCC biology, hypoxia-inducible factor regulation, and therapeutic vulnerabilities. The adherent 786-O line exhibits stable growth characteristics compatible with standard cell culture protocols and high-throughput assay formats.
DTX3L encodes an E3 ubiquitin ligase that functions at the intersection of Notch signaling, DNA damage response, and antiviral interferon pathways. It is activated downstream of interferon alpha/beta/gamma and STAT1/STAT2 signaling, interacting directly with PARP9, STAT1, IRF9, and the Notch receptor intracellular domain. DTX3L promotes ubiquitination of histones and ISG15, thereby modulating protein stability and recruitment at damaged chromatin and signalosomes.
In the DNA damage response, DTX3L-mediated ubiquitination facilitates assembly of repair complexes, while in interferon signaling, it contributes to ISGylation and transcriptional regulation through IRF9. Disruption of DTX3L in the 786-O ccRCC background impairs ubiquitin-dependent signaling cascades that are critical for DNA repair and interferon-mediated antiviral and inflammatory responses. The VHL-mutant environment provides a disease-relevant context to study how loss of DTX3L affects tumor cell survival, genomic stability, and sensitivity to DNA-damaging agents.
This model thus enables dissection of DTX3L??s contributions to oncogenic processes and therapeutic resistance in renal cell carcinoma. Researchers can employ this knockout polyclonal population to investigate DTX3L function in renal cell carcinoma, elucidate mechanisms of DNA damage repair, explore crosstalk between Notch and interferon signaling, and validate DTX3L as a potential therapeutic target. Representative applications include western blotting, RT-qPCR, RNA-seq, immunofluorescence, gamma-H2AX foci formation assays, cell viability measurements, and flow cytometry-based apoptosis detection. For further details, please contact Ascent Research.
