The DNPH1 Knockout SK-OV-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the SK-OV-3 human ovarian adenocarcinoma cell line. This product provides a heterogeneous pool of cells carrying targeted disruptions in the DNPH1 gene, generating a loss-of-function model for studying deoxynucleoside 5??-monophosphate N-glycosidase activity. The polyclonal format preserves functional diversity within the population while enabling pooled analysis of DNPH1-dependent phenotypes, avoiding clonal artifacts.
The parental SK-OV-3 cell line was established from the ascites of a 64-year-old female with ovarian adenocarcinoma and serves as a well-characterized model for human ovarian cancer. These cells exhibit epithelial morphology, are hypodiploid, and harbor a TP53 null mutation with concomitant HER2 overexpression, rendering them tumorigenic in vivo. SK-OV-3 thus represents an aggressive, p53-deficient background relevant to high-grade serous ovarian carcinoma research.
DNPH1 encodes a deoxynucleoside 5??-monophosphate N-glycosidase that hydrolyzes 2??-deoxyribonucleoside 5??-monophosphates, regulating dNTP pools. Acting downstream of TP53 and DNA damage signaling, DNPH1 cooperates with ribonucleotide reductase and replication fork proteins to sustain nucleotide homeostasis and replication fidelity. DNPH1 loss disrupts dNTP balance, impairing DNA polymerase function and triggering replication stress, which can activate caspase-mediated apoptosis.
In the TP53-null SK-OV-3 context, DNPH1 knockout enables dissection of p53-independent mechanisms governing nucleotide metabolism and genomic stability in ovarian cancer cells. The model is suited to investigating how dNTP pool perturbations influence DNA repair capacity and apoptotic thresholds in HER2-overexpressing tumor cells, and may reveal synthetic lethal vulnerabilities exploitable with nucleoside analogs or platinum-based chemotherapies.
Researchers can employ this polyclonal knockout population to examine DNPH1??s role in ovarian cancer cell fitness, DNA damage sensitization, and chemosensitivity. Assays include western blotting for DNPH1 and apoptosis markers, RT?qPCR, cell viability (MTT) and clonogenic assays, annexin V staining, nucleotide quantification by LC?MS, and immunofluorescence for ??H2AX and RAD51. Drug profiling with cisplatin or gemcitabine assesses DNPH1-dependent responses. For technical inquiries, please contact Ascent Research.
