DNASE1L1 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 786-O human renal cell carcinoma line. The DNASE1L1 gene, which encodes a deoxyribonuclease involved in DNA degradation and apoptosis, has been disrupted using CRISPR/Cas9 to generate a loss-of-function model. This polyclonal pool offers a heterogeneous population with targeted gene disruption, suitable for studying gene function in a cancer context without clonal selection, thereby preserving diverse genetic backgrounds while maintaining DNASE1L1 knockout.
786-O is a widely used VHL-mutant clear cell renal cell carcinoma (ccRCC) cell line exhibiting adherent epithelial morphology. Originating from a primary renal adenocarcinoma, 786-O cells harbor a homozygous VHL mutation leading to constitutive HIF activation, mimicking key features of ccRCC. This cell line serves as a standard model for renal cancer research, particularly in studies of hypoxia signaling, tumorigenesis, and therapeutic response.
DNASE1L1 encodes a Ca2+/Mg2+-dependent DNA endonuclease that mediates chromatin breakdown during apoptosis. The protein functions downstream of apoptotic stimuli and caspase-3 activation, working in concert with DNA fragmentation factor (DFFB/CAD) and its inhibitor ICAD. Under physiological conditions, DNASE1L1 promotes internucleosomal DNA cleavage and nucleosome release, facilitating clearance of apoptotic debris. It interacts with actin and serum cofactors, and its activity is regulated by p53-dependent pathways. Thus, DNASE1L1 is a key executor of DNA degradation in programmed cell death.
In 786-O cells, DNASE1L1 knockout is expected to impair apoptosis-associated DNA degradation and chromatinolysis, potentially altering cellular responses to genotoxic stress or apoptotic inducers. Given the VHL-mutant background, these polyclonal knockout cells enable investigation of crosstalk between hypoxia-driven survival pathways and DNA damage responses. The model may reveal how loss of DNA degradation capability influences ccRCC cell survival, drug sensitivity, or immune clearance, with implications for understanding resistance to apoptosis in renal cancer.
This product is applicable in diverse functional genomics studies. Researchers can assess apoptosis regulation via caspase activity assays, TUNEL staining, and DNA fragmentation analysis. The knockout model enables examination of DNASE1L1’s role in nucleosome release and clearance of apoptotic debris using immunofluorescence and Western blotting. Moreover, drug sensitivity testing and cell viability assays can evaluate chemotherapeutic responses in the context of impaired DNA degradation. The polyclonal population is ideal for investigating genetic interactions or clonal heterogeneity in ccRCC. For further details, contact Ascent Research.
