The DNPH1 Knockout MES-OV Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed for loss-of-function studies of the DNPH1 gene. Generated via CRISPR/Cas9-mediated target-gene disruption in the MES-OV human ovarian adenocarcinoma epithelial cell line, this polyclonal knockout model provides a genetically diverse and robust system for investigating DNPH1 function in nucleotide metabolism and DNA damage responses.
The MES-OV cell line is derived from human ovarian adenocarcinoma and is widely used in ovarian cancer research to study tumor biology, chemoresistance, and oxidative stress responses. Retaining key characteristics of high-grade serous ovarian carcinoma, MES-OV offers a clinically relevant epithelial model for exploring how nucleotide pool sanitization impacts malignant progression and drug resistance.
DNPH1 encodes a homodimeric hydrolase that cleaves oxidized deoxynucleoside triphosphates, notably 8-oxo-dGTP, preventing their incorporation into DNA. Its expression is transcriptionally activated by NFE2L2 (NRF2) in response to reactive oxygen species (ROS), forming a critical oxidative stress defense mechanism. DNPH1 activity reduces cellular 8-oxo-dGTP levels, diminishes 8-oxoguanine incorporation, and suppresses mutagenesis, thereby maintaining genomic integrity. The enzyme may functionally interact with NUDT1 (MTH1) to cooperatively sanitize the nucleotide pool.
In ovarian adenocarcinoma, DNPH1-mediated nucleotide sanitization likely counteracts oxidative stress inherent to the tumor microenvironment and mitigates genotoxic effects of certain chemotherapies. DNPH1 knockout in MES-OV cells may uncover dependencies on alternative repair pathways and could sensitize cells to ROS-inducing agents or antioxidant signaling inhibitors. Thus, the polyclonal knockout pool is a valuable tool for dissecting the role of nucleotide sanitization in genomic stability, oxidative stress survival, and chemoresistance in epithelial ovarian cancer.
Researchers can utilize these cells to explore nucleotide metabolism and DNA damage response pathways using assays such as dNTP pool quantification by LC-MS, alkaline comet assay for DNA strand breaks, ??H2AX immunostaining for double-strand breaks, and NRF2 reporter assays for oxidative stress signaling. Additional applications include drug sensitivity profiling, ROS measurement with fluorescent probes, and complementation studies with wild-type or mutant DNPH1. For further information, please contact Ascent Research.
