The DNPH1 Knockout TE1 Polyclonal Cells are a human CRISPR/Cas9-edited polyclonal knockout cell population generated from the TE1 esophageal squamous cell carcinoma cell line. This product provides a loss-of-function model for studying DNPH1 in a cancer-relevant epithelial background. The polyclonal nature captures the heterogeneity of editing outcomes, enabling robust population-level analyses.
The TE1 cell line was derived from a patient with esophageal squamous cell carcinoma and is widely employed as a model for esophageal cancer research. These cells exhibit typical epithelial morphology and retain molecular characteristics of squamous cell carcinoma, making them suitable for investigating oncogenic signaling and tumor biology. The integration of CRISPR-mediated gene disruption in this line allows the dissection of gene function in a disease-relevant context.
DNPH1 (Rcl) encodes a nucleotide hydrolase that is transcriptionally activated by the c-Myc transcription factor. It dephosphorylates modified nucleotide triphosphates such as 5-methyl-dCTP, preventing their erroneous incorporation into DNA. By eliminating aberrant nucleotides, DNPH1 preserves genomic integrity and influences DNA methylation patterns indirectly through substrate availability. Knockout of DNPH1 disrupts this clearance mechanism, leading to accumulation of modified nucleotides, which can trigger DNA damage response pathways involving kinases such as ATM and ATR. Thus, DNPH1 functions downstream of c-Myc and upstream of DNA damage signaling, linking oncogenic proliferation to nucleotide sanitation.
In TE1 cells, loss of DNPH1 is anticipated to perturb nucleotide metabolism, potentially causing DNA damage and activation of the DDR, which may affect cell proliferation and survival. Given the central role of c-Myc in esophageal squamous cell carcinoma, this knockout model provides a unique tool to study the consequences of impaired nucleotide hydrolysis in a c-Myc-driven cancer context. It enables investigation of how nucleotide pool imbalances contribute to genomic instability and chemosensitivity.
Typical applications include functional investigation of nucleotide metabolism, DNA damage responses, and c-Myc downstream signaling in esophageal cancer. Researchers can employ this model to perform western blotting for DNPH1 and DNA damage markers (e.g., ??H2AX), RT-qPCR to assess target gene expression, nucleotide pool analysis by mass spectrometry, bisulfite sequencing for DNA methylation profiling, cell proliferation and apoptosis assays, phospho-signaling analysis of ATM/ATR, and immunofluorescence for DNA damage foci. The polyclonal knockout population is also well-suited for drug sensitivity profiling against chemotherapeutics or targeted agents. For further information or technical inquiries, please contact Ascent Research.
