The APOBEC3A Knockout NCI-H1703 Polyclonal Cells product consists of a CRISPR/Cas9-edited polyclonal population of NCI-H1703 human lung squamous carcinoma cells with targeted disruption of the APOBEC3A gene. This loss-of-function model ablates endogenous APOBEC3A cytidine deaminase activity, enabling dissection of its roles in mutagenesis and innate immunity within a well-characterized cancer background.
NCI-H1703 is an adherent epithelial cell line established from a primary lung squamous cell carcinoma of a 54-year-old male smoker. It harbors TP53 mutations and additional oncogenic lesions, faithfully recapitulating non-small cell lung cancer (NSCLC) biology. Widely utilized in lung cancer research, this line provides a relevant host for studying APOBEC3A in tumor evolution and drug response.
APOBEC3A encodes a single-stranded DNA cytidine deaminase that edits cytosine to uracil, generating C-to-T transitions and DNA breaks. Its expression is transcriptionally activated by interferon-?? (IFN-??), interferon-?? (IFN-??), and tumor necrosis factor-?? (TNF-??) via JAK/STAT signaling, as well as by DNA damage-induced ATM/ATR kinase activity. APOBEC3A interacts with replication protein A (RPA) and proliferating cell nuclear antigen (PCNA) to access ssDNA substrates. The resulting uracils are processed by uracil DNA glycosylase (UNG) and APE1 endonuclease, creating abasic sites and strand breaks that trigger ATM/ATR/p53/p21 checkpoint signaling. Through these mechanistic steps, APOBEC3A exerts dual functions in viral restriction and cancer mutagenesis.
In NCI-H1703 cells, endogenous APOBEC3A activity promotes C-to-T mutagenesis and genomic instability, contributing to tumor heterogeneity. Its knockout in this TP53-mutant context eliminates confounding deaminase activity, allowing precise investigation of APOBEC3A-driven mutagenic processes and their interaction with defective p53-dependent DNA damage responses.
Researchers can apply these polyclonal knockout cells in loss-of-function studies addressing lung cancer mutagenesis, innate immunity, and viral restriction. Suitable assays include Western blot and RT-qPCR for expression analysis, next-generation sequencing for mutation signature profiling, and functional readouts such as colony formation, migration, and drug sensitivity screening (e.g., cisplatin, PARP inhibitors). DNA damage can be assessed via ??H2AX immunofluorescence and comet assay, while apoptosis is quantifiable by Annexin V/PI flow cytometry. This model supports preclinical evaluation of APOBEC3A inhibitors and exploration of therapeutic combinations. For additional technical details and ordering information, please contact Ascent Research.
