This product is a CRISPR/Cas9-edited polyclonal knockout cell population of the NCI-H1975 human lung adenocarcinoma line, with targeted disruption of the INO80C gene. The polyclonal format provides a heterogeneous pool of edited alleles, enabling robust loss-of-function studies without single-cell cloning artifacts.
NCI-H1975 is a widely used non-small cell lung cancer (NSCLC) model derived from a patient with adenocarcinoma. It harbors an activating EGFR L858R mutation and serves as a key platform for investigating oncogenic signaling, drug resistance pathways, and chromatin regulation in epithelial cancer biology.
The INO80C protein is a core subunit of the ATP-dependent INO80 chromatin remodeling complex, which evicts or slides nucleosomes to modulate DNA accessibility. Upstream, it is activated by ATM and ATR kinases at DNA double-strand breaks. INO80C interacts with complex components such as INO80, ACTL6A, RUVBL1, and RUVBL2, and facilitates homologous recombination repair by recruiting RAD51 and BRCA1. It also regulates gene expression by influencing histone modifications and RNA polymerase II activity. Consequently, INO80C disruption impairs DNA damage repair and alters transcriptional programs.
In NCI-H1975 cells, loss of INO80C compromises homologous recombination repair, sensitizing cells to genotoxic stress and potentially revealing synthetic lethal relationships with other repair deficiencies. For example, defective chromatin remodeling downstream of EGFR signals may alter the expression of DNA repair genes, offering insights into therapy-driven resistance mechanisms. Given the EGFR-mutant background, this model is ideal for studying how INO80-mediated chromatin remodeling influences tumor cell proliferation, survival, and resistance to targeted therapies. It enables dissection of crosstalk between DNA repair pathways and oncogenic signaling.
These polyclonal knockout cells are suited for chromatin biology, DNA damage response studies, and functional genomics. Compatible assays include ??H2AX immunofluorescence, comet assay, homologous recombination reporter systems, cell viability and proliferation assays, RNA-seq, ChIP-qPCR for histone modifications, and drug sensitivity profiling. Researchers can investigate synthetic lethality with PARP inhibitors or explore mechanisms governing NSCLC drug resistance. For further information, please contact Ascent Research.
