The DNPH1 Knockout 769-P Polyclonal Cells are a polyclonal knockout population of human clear cell renal cell carcinoma (ccRCC) 769-P cells, created by CRISPR/Cas9-mediated disruption of the DNPH1 gene. This product is provided as a heterogeneous pool of edited cells without clonal isolation, suitable for loss-of-function studies in a population context.
The parental 769-P cell line is a well-established model of ccRCC, characterized by a homozygous mutation in the von Hippel-Lindau (VHL) tumor suppressor gene. Loss of functional VHL results in constitutive stabilization of hypoxia-inducible factors (HIFs), driving a pseudo-hypoxic state that reprograms cellular metabolism, promotes angiogenesis, and enhances tumor growth. This genetic background makes 769-P an appropriate host for studying metabolic vulnerabilities in renal cancer, particularly those intersecting with nucleotide metabolism and oncogenic signaling.
DNPH1 (2′-deoxynucleoside 5′-phosphate N-hydrolase 1) catalyzes the hydrolysis of deoxyribonucleoside 5′-monophosphates (dNMPs) into free nucleobases and deoxyribose 5-phosphate, a central step in pyrimidine and purine deoxynucleoside salvage. The enzyme is directly regulated by the MYC oncoprotein, linking nucleotide metabolism to MYC-driven proliferative programs. Substrates include dAMP, dCMP, dGMP, and dTMP; the reaction products modulate dNTP pool sizes, thereby influencing DNA replication fidelity and cell cycle progression. In the 769-P ccRCC context, the MYC-DNPH1 signaling node may contribute to metabolic adaptation under the pseudo-hypoxic conditions induced by VHL loss.
Loss of DNPH1 in this polyclonal knockout model is predicted to impair nucleotide salvage, causing dNTP imbalances that may restrict the high proliferative demand of ccRCC cells. Given the VHL-deficient, HIF-activated background, this model enables dissection of how nucleotide salvage intersects with oncogenic metabolic rewiring. It offers a platform to explore context-specific dependencies on salvage pathways and validate the role of MYC targets in maintaining nucleotide homeostasis under hypoxic stress.
Researchers can use these cells for quantifying dNTP pools via LC-MS, proliferation and viability assays under nucleotide stress, and antimetabolite drug sensitivity screening. The population is also suitable for MYC target validation using Western blotting and RT-qPCR, and cell cycle analysis by flow cytometry. For technical support and product details, contact Ascent Research.
