The DNPH1 Knockout LoVo Polyclonal Cells are a polyclonal population derived from the LoVo cell line with CRISPR/Cas9-mediated disruption of the DNPH1 gene. This polyclonal knockout model offers a heterogeneous loss-of-function background, avoiding single-cell clonal artifacts. DNPH1 encodes a deoxynucleoside triphosphatase that hydrolyzes dNTPs, regulating nucleotide pools essential for DNA replication. This product is designed for studies of nucleotide metabolism and DNA replication fidelity in a colorectal adenocarcinoma context.
LoVo cells are a human metastatic colorectal adenocarcinoma line derived from the supraclavicular lymph node metastasis of a 56-year-old male patient. They serve as a model for advanced colorectal cancer, featuring aberrant c-Myc signaling and proliferative capacity. The metastatic nature of LoVo cells makes them relevant for investigating tumor progression and therapeutic resistance.
DNPH1 catalyzes the hydrolysis of deoxynucleoside triphosphates (dNTPs), thereby modulating intracellular dNTP pools. This function is tightly linked to c-Myc, which transcriptionally activates DNPH1, coupling nucleotide supply to proliferative demand. DNPH1 interacts with ribonucleotide reductase (RNR) subunits RRM1 and RRM2, key enzymes in de novo dNTP synthesis. Downstream, DNPH1 influences dNTP substrate availability for DNA polymerases. In colorectal cancer cells, the c-Myc?CDNPH1?CRNR axis integrates oncogenic signaling with nucleotide metabolism, ensuring adequate DNA precursors for rapid cell division.
In the LoVo colorectal adenocarcinoma model, DNPH1 knockout disrupts dNTP homeostasis, potentially impairing DNA replication and activating DNA damage responses. Given the c-Myc-driven nature of these cells, this model enables dissection of DNPH1’s role in oncogenic nucleotide metabolism. Researchers can explore how DNPH1 deficiency affects cell cycle progression, replication stress, and sensitivity to antimetabolites, as well as possible compensatory pathways.
Typical applications include western blotting and RT-qPCR for knockout validation, cell proliferation and colony formation assays, dNTP quantification, flow cytometry for cell cycle analysis, and ??H2AX immunofluorescence to assess DNA damage. Drug sensitivity screens can identify vulnerabilities in nucleotide metabolism pathways. For inquiries, please contact Ascent Research.
