This product is a CRISPR/Cas9-edited polyclonal knockout cell population targeting DNPH1 in HAP1 cells. The polyclonal format provides a heterogeneous mixture of cells with diverse loss-of-function alleles, enabling robust assessment of gene disruption effects at the population level. It is designed for functional genomics studies requiring broad representation of knockout phenotypes, such as chemosensitivity screens and pathway analyses.
HAP1 cells are a near-haploid human cell line derived from KBM-7 chronic myeloid leukemia. Their haploid karyotype simplifies genetic analysis and facilitates clean genotype-to-phenotype mapping. This leukemic background provides a disease-relevant model for studying cancer cell biology, particularly processes linked to nucleotide metabolism, proliferation, and drug response.
DNPH1 encodes a deoxynucleoside triphosphate hydrolase that catalyzes hydrolysis of dNTPs (dATP, dGTP, dCTP, dTTP) to dNMPs, regulating intracellular nucleotide pools. As a direct transcriptional target of c-Myc, DNPH1 expression is activated by c-Myc signaling. DNPH1 functions as a homodimer and acts upstream of ribonucleotide reductase and DNA polymerases. Through modulation of dNTP availability, DNPH1 influences DNA replication fidelity, cell cycle progression, and genotoxic stress responses. Its disruption perturbs nucleotide precursor balance, affecting genome stability and proliferation.
In HAP1 cells, DNPH1 knockout elevates dNTP pools, potentially causing replication stress and altering sensitivity to nucleoside analogs. This model enables dissection of c-Myc-driven oncogenesis and chemoresistance mechanisms. The haploid background ensures phenotype alterations are directly attributed to DNPH1 disruption without confounding alleles.
Applications include functional genomics, cancer cell biology, nucleotide metabolism studies, and chemosensitivity screening with agents like 5-fluorouracil or gemcitabine. Representative assays: western blotting for DNPH1 and c-Myc, RT-qPCR, dNTP pool quantification, cell viability assays, flow cytometry for cell cycle, and proliferation assays. For further details, contact Ascent Research.
