The DTX3L Knockout MES-OV Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population of the MES-OV human ovarian clear cell carcinoma cell line, designed to disrupt the DTX3L gene. This mixed population features heterogeneous NHEJ-mediated gene disruptions, providing a robust loss-of-function model without clonal selection artifacts, suitable for pooled functional genomic experiments and drug sensitivity screens in ovarian cancer research.
MES-OV is an adherent epithelial cell line established from a patient-derived ovarian clear cell carcinoma, a subtype often resistant to conventional platinum-based chemotherapy. The line retains epithelial morphology and genomic features of the original tumor, making it a representative platform for studying ovarian cancer biology. DTX3L disruption in this background enables targeted investigation of ubiquitin ligase functions in a clinically relevant model.
DTX3L encodes an E3 ubiquitin ligase that forms a complex with PARP9 to catalyze K63-linked polyubiquitination, essential for DNA damage signaling and interferon-dependent antiviral immunity. At DNA double-strand breaks, activated by ATM, DTX3L promotes ubiquitination of histone H2B, facilitating 53BP1 recruitment, and interacts with BRCA1/BARD1 and UBE2N. Downstream of interferon-??/??, the IFNAR1-JAK1-STAT1 axis induces DTX3L expression, linking it to immune signaling. Downstream, DTX3L-mediated ubiquitination targets histone H2B and modulates 53BP1 functions. This dual role positions DTX3L at the intersection of genome stability and innate immunity.
In the MES-OV background, DTX3L knockout provides a model to investigate convergence of DNA repair and interferon pathways often deregulated in ovarian clear cell carcinoma. Researchers can examine impacts on cisplatin sensitivity and explore how loss of DTX3L-mediated ubiquitination alters DNA damage response or interferon-stimulated gene programs. Moreover, the model facilitates functional analysis of interferon signaling in tumor cells, where DTX3L-dependent ubiquitination may regulate STAT1 phosphorylation or expression of interferon-stimulated genes, potentially uncovering therapeutic liabilities.
Applications include immunofluorescence for ??H2AX foci to monitor DNA repair, comet assays, cell viability assays with cisplatin, flow cytometry for phospho-STAT1, western blotting, and colony formation. These assays enable detailed mechanistic studies and preclinical evaluation of targeted therapies. The polyclonal population demands validation but offers diverse editing outcomes. Researchers are encouraged to contact Ascent Research for technical support and additional product information.
