The FIRRM Knockout SK-HEP-1 Polyclonal Cells provide a CRISPR/Cas9-edited polyclonal knockout cell population in which FIRRM gene disruption has been introduced into the SK-HEP-1 human liver adenocarcinoma cell line. This product offers a loss-of-function model for studying FIRRM-dependent processes in a hepatocellular carcinoma context. The heterogeneous polyclonal pool allows researchers to assess the functional consequences of FIRRM ablation across a population of cells, reflecting the genetic diversity typical of tumor biology. Stable, expanding cultures are readily established, making this model suitable for routine functional assays, drug response profiling, and mechanistic investigations into DNA repair pathways.
SK-HEP-1 is a well-characterized epithelial tumor cell line originally derived from a hepatocellular carcinoma. It maintains hallmark features of liver adenocarcinoma, including anchorage-independent growth and tumorigenicity in xenograft models, and is widely employed in liver cancer research. The cell line retains intact DNA damage response machinery, making it an appropriate host for studying homologous recombination repair and genomic stability. Its genetic background provides a relevant context for exploring how disruption of repair factors such as FIRRM influences cancer cell survival, proliferation, and therapeutic sensitivity.
FIRRM (also known as C1orf112) is a recently characterized regulator of homologous recombination repair, a high-fidelity pathway for resolving DNA double-strand breaks. Mechanistically, FIRRM interacts directly with FIGNL1 and facilitates the recruitment of RAD51 to damaged sites, a critical step for strand invasion and homology search. Upstream, the kinases ATM and ATR are activated by DNA double-strand breaks and phosphorylate downstream effectors including CHK2 and RPA, initiating the repair cascade. FIRRM functions in concert with BRCA2 to promote efficient RAD51 filament formation. Loss of FIRRM disrupts RAD51 focus formation, impairing homologous recombination and leading to unresolved breaks, chromosomal aberrations, and heightened sensitivity to DNA-damaging agents. The pathway also involves RPA, RAD51, BRCA2, and FIGNL1 as core components.
In the SK-HEP-1 hepatocellular carcinoma model, FIRRM depletion creates a DNA repair-deficient background that is particularly informative for studying genomic instability and synthetic lethality. Liver cancers frequently exhibit replication stress and altered DNA damage responses; thus, FIRRM knockout cells may reveal vulnerabilities exploitable by PARP inhibitors or other DNA-damaging chemotherapeutics. This model enables investigation of how loss of FIRRM-mediated RAD51 recruitment interacts with oncogenic signaling pathways prevalent in HCC. It also serves as a platform to examine compensatory repair mechanisms that cancer cells may activate when homologous recombination is compromised.
Typical applications include DNA damage repair studies using clonogenic survival assays after ionizing radiation or genotoxic drugs, immunofluorescence microscopy to quantify RAD51 foci formation, and co-immunoprecipitation experiments to probe FIRRM-FIGNL1-RAD51 complex dynamics. Additional uses encompass synthetic lethality screening with DNA repair inhibitors, cell cycle analysis by flow cytometry following damage, and HR reporter assays to measure recombination efficiency. These assays support discovery of resistance mechanisms and identification of therapeutic targets in homologous recombination-deficient tumors. For further details, please contact Ascent Research.
