The KIAA1191 Knockout A-549 Polyclonal Cells product provides a heterogeneous population of A-549 human lung adenocarcinoma epithelial cells harboring CRISPR/Cas9-mediated disruption of the KIAA1191 locus. Generated as a polyclonal pool without clonal isolation, these cells offer a genetically diverse knockout model that avoids the potential biases of single-cell-derived lines while maintaining robust performance in DNA damage response and repair assays. This format is particularly suitable for studies where population-level heterogeneity recapitulates the variable penetrance of repair defects observed in tumor biology.
The host A-549 cell line was originally established from a human lung adenocarcinoma and serves as a well-characterized model of non-small cell lung cancer. These adherent epithelial cells are p53 wild-type and harbor an activating KRAS(G12S) mutation, making them a valuable platform for investigating oncogenic signaling and therapeutic sensitivities. A-549 cells exhibit alveolar type II pneumocyte features, including surfactant protein expression, and their robust proliferation in standard cultures facilitates reproducible, high-throughput experimental workflows.
KIAA1191 encodes a DNA damage response protein rapidly recruited to double-strand breaks, where it interacts with PARP1 and XRCC1 to facilitate repair. Upstream, genotoxic stress activates ATM and ATR kinases, which phosphorylate H2AX (??H2AX) and coordinate repair factor assembly. KIAA1191 acts downstream of these kinases, stabilizing protein interactions at damage sites to promote base excision and homologous recombination repair. Its disruption impairs XRCC1 recruitment, causing persistent ??H2AX foci and compromised DNA repair.
In the A-549 lung adenocarcinoma background, KIAA1191 knockout synergizes with the endogenous KRAS mutation to exacerbate genomic instability, providing a powerful model to study the role of DNA repair defects in tumor progression. This system enables investigation of synthetic lethal interactions, particularly with PARP inhibitors, and can be used to dissect mechanisms of acquired chemoresistance. The polyclonal knockout format also permits examination of how heterogeneous repair capacity influences clonal dynamics and fitness under selective pressure from genotoxic therapies.
Typical applications include mechanistic dissection of DNA damage signaling, high-throughput screening of DNA repair modulators, and preclinical evaluation of PARP inhibitor sensitivity. The cells can be analyzed by Western blotting, RT-qPCR, and ??H2AX immunofluorescence to confirm gene disruption and monitor DNA damage. Functional assays such as the alkaline comet assay, colony formation assay, and drug sensitivity profiling provide quantitative endpoints for DNA repair activity and cellular survival. For further product information, please contact Ascent Research.
