The INIP Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population derived from the NCI-H1975 lung adenocarcinoma cell line with targeted disruption of INIP. This polyclonal knockout pool provides a loss-of-function model for studying INIP-mediated DNA damage response and homologous recombination repair pathways, allowing assessment of gene disruption effects without clonal selection bias.
The parental NCI-H1975 cell line is a well-characterized epithelial model of non-small cell lung cancer (NSCLC), originally derived from a lung adenocarcinoma. These cells harbor activating EGFR mutations (L858R and T790M), which promote tumorigenic signaling and confer resistance to first-generation EGFR tyrosine kinase inhibitors. As an adherent, tumorigenic cell line, NCI-H1975 provides a clinically relevant platform for studying DNA repair pathways under oncogenic stress and exploring targeted therapy vulnerabilities.
INIP is an essential subunit of the sensor of single-stranded DNA (SOSS) complex, which detects DNA double-strand breaks (DSBs) and initiates repair signaling. INIP directly interacts with INTS3, NABP1, and NABP2 to facilitate the assembly of repair complexes at damage sites. Following DSB induction, ATM and ATR kinases activate a cascade wherein SOSS complexes promote homologous recombination by supporting the recruitment of RAD51, BRCA1, and BRCA2. INIP disruption therefore impairs accurate DSB repair, leading to persistent DNA lesions, genomic instability, and increased reliance on error-prone repair pathways.
In the NCI-H1975 background, INIP knockout generates a model of compromised DNA repair in an EGFR-mutant lung cancer context, which is inherently susceptible to genomic instability. The concurrent loss of homologous recombination capacity and oncogenic EGFR signaling enhances sensitivity to DNA-damaging agents and PARP inhibitors, enabling investigation of synthetic lethal relationships and DNA repair?Ctargeted therapies in NSCLC.
These polyclonal knockout cells are suitable for a variety of functional assays, including western blotting and immunofluorescence to verify INIP disruption and downstream marker expression, ??H2AX foci assays to monitor DNA damage accumulation, homologous recombination reporter assays to quantify repair efficiency, and cell viability assays using DNA-damaging agents such as cisplatin or PARP inhibitors to assess chemosensitivity. They facilitate investigations into lung cancer biology, DNA repair dynamics, drug response profiling, and synthetic lethal interactions, providing a versatile model for preclinical NSCLC research. For further product information or technical support, please contact Ascent Research.
