The ATM Knockout A-549 Polyclonal Cells product provides a pooled population of A-549 lung adenocarcinoma epithelial cells that have been engineered via CRISPR/Cas9-mediated disruption of the ATM gene. This polyclonal knockout model encompasses a heterogeneous mixture of ATM loss-of-function genotypes, reflecting diverse mutational outcomes and minimizing clonal artifact. The use of CRISPR/Cas9 technology enables targeted gene disruption, producing a versatile loss-of-function model for studying ATM-dependent processes in a relevant cancer cell background.
The A-549 cell line was originally established from explant culture of lung adenocarcinoma tissue obtained from a 58-year-old male. These cells display epithelial morphology and retain features characteristic of non-small cell lung cancer, including wild-type p53 status and sensitivity to DNA-damaging agents. A-549 cells are extensively utilized in cancer biology research, drug development, and radiobiology, making them an ideal host for investigating the tumor-suppressive and DNA repair functions of ATM in a lung adenocarcinoma context.
The ATM gene encodes a 370 kDa serine/threonine kinase that serves as a master orchestrator of the response to DNA double-strand breaks. ATM is recruited and activated by the MRN complex (MRE11?CRAD50?CNBS1) at damage sites, after which it phosphorylates substrates including p53, CHK2, H2AX, BRCA1, and 53BP1. These phosphorylation events trigger cell cycle checkpoints (G1/S, intra-S, and G2/M), promote DNA repair through homologous recombination and non-homologous end joining, and initiate apoptosis if damage is irreparable. ATM also interacts with ATR, DNA-PKcs, and MDC1, integrating genomic stress signals.
In the A-549 lung adenocarcinoma model, CRISPR/Cas9-mediated disruption of ATM provides a valuable tool for studying DNA damage signaling in an epithelial cancer context. ATM mutations and reduced expression have been associated with lung cancer risk and therapeutic response, making this knockout population suitable for dissecting how ATM loss affects sensitivity to ionizing radiation, platinum agents, and DNA repair inhibitors. The polyclonal nature avoids the selection bias of clonal isolation, preserving a broader spectrum of biological behaviors relevant to tumor heterogeneity.
This ATM knockout polyclonal population supports a range of functional assays, including immunoblotting for phospho-ATM substrates, immunofluorescence detection of ??H2AX and 53BP1 foci, flow cytometric cell cycle analysis, apoptosis quantification, and clonogenic survival after irradiation or drug treatment. It is also suitable for high-throughput drug sensitivity screens to uncover ATM-dependent vulnerabilities. The model facilitates detailed dissection of ATM signaling and testing of DNA damage response modulators. For further information or technical support, please contact Ascent Research.
