The ATM Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population of the human SK-HEP-1 hepatocellular carcinoma cell line, designed to disrupt the ATM gene. This heterogeneous pool comprises a mixture of edited alleles, avoiding clonal selection artifacts while faithfully recapitulating ATM loss-of-function. Supplied as a cryopreserved stock, the product is ready for immediate use in DNA damage response and liver cancer research.
The SK-HEP-1 parental line was established from ascitic fluid of a patient with liver adenocarcinoma and serves as a classic model of cancerous hepatic epithelium. It is widely employed to investigate hepatocarcinogenesis, tumor microenvironment interactions, and therapeutic resistance. The knockout derivative preserves the parental line??s biological context, enabling focused analysis of ATM-dependent pathways in hepatocellular carcinoma.
ATM encodes a serine/threonine kinase that acts as a master regulator of DNA double-strand break (DSB) signaling. Recruitment by the MRE11-RAD50-NBS1 (MRN) complex and autophosphorylation activate ATM, which then phosphorylates downstream effectors including checkpoint kinase 2 (CHK2) and p53 to impose cell cycle arrest. Additionally, ATM phosphorylates BRCA1 and H2AX to coordinate homologous recombination and non-homologous end joining repair. The kinase also interfaces with ATR, DNA-PKcs, and 53BP1 to balance repair pathway choice and apoptosis. Upstream, ATM is modulated by oxidative stress and TIP60, while phosphatases PP2A and Wip1 provide feedback regulation.
In liver cancer, ATM loss is associated with genomic instability, enhanced aggressiveness, and altered drug sensitivity, making this knockout model highly relevant for hepatocellular carcinoma research. By comparing the polyclonal knockout pool to parental SK-HEP-1 cells, investigators can dissect how ATM deficiency influences tumor growth, metastatic potential, and response to DNA-damaging agents or DDR inhibitors like PARP inhibitors.
Key applications include radiosensitivity and chemosensitivity profiling via clonogenic survival and comet assays, cell cycle analysis by flow cytometry, and apoptosis measurement with Annexin V/PI staining. ATM signaling status is routinely assessed by western blot for phospho-ATM (Ser1981) and phospho-CHK2, and by ??-H2AX immunofluorescence. The model also supports RT-qPCR-based DDR gene expression studies and drug screening. For additional information, contact Ascent Research.
