The KAT7 Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from A-549 human lung adenocarcinoma epithelial cells. This model features targeted disruption of the KAT7 gene, which encodes a histone acetyltransferase essential for DNA replication licensing and cell cycle progression. The polyclonal format provides a heterogeneous knockout pool, enabling the study of gene function without clonal selection biases. Designed for biomedical research, these cells serve as a loss-of-function tool to investigate KAT7-dependent processes in lung adenocarcinoma.
A-549 cells are an immortalized human alveolar basal epithelial cell line isolated from a 58-year-old Caucasian male with lung carcinoma. They are widely used as a model for human lung adenocarcinoma, offering a reproducible system for studying tumor biology, drug responses, and molecular mechanisms. The cells retain key epithelial characteristics and are amenable to genetic manipulation, making them suitable for CRISPR/Cas9-mediated knockout studies. The A-549 background provides a clinically relevant context for exploring KAT7’s role in lung cancer pathogenesis.
KAT7 functions as the catalytic subunit of the HBO1 acetyltransferase complex, which includes JADE1, ING4, and MEAF6. It acetylates histone H4 at lysines 5, 8, and 12 (H4K5/K8/K12) and histone H3 at lysine 14 (H3K14) to facilitate chromatin relaxation at replication origins. This activity is regulated by CDK1 and CDK2 kinases during the G1/S transition, promoting chromatin loading of the MCM2-7 helicase complex via interactions with CDT1 and the ORC1-6 complex. KAT7 also acetylates p53 at K120, influencing the DNA damage response and apoptosis. Loss of KAT7 disrupts origin firing, leading to replication stress, impaired cell cycle progression, and altered p53 signaling. The knockout cells allow dissection of these molecular interactions and their downstream effects on DNA replication and cell fate.
In A-549 lung adenocarcinoma cells, KAT7 knockout provides insights into replication licensing mechanisms and their relevance to cancer proliferation. KAT7 is implicated in tumorigenesis through its roles in DNA repair and cell cycle control, and its disruption may sensitize cells to replication stress or genotoxic agents. The polyclonal population recapitulates the heterogeneity of tumor cells, enabling studies of clonal variation in response to KAT7 loss. This model is valuable for identifying synthetic lethal interactions and evaluating KAT7 as a potential therapeutic target in lung adenocarcinoma and other KAT7-associated malignancies.
Research applications include investigating DNA replication dynamics using DNA fiber assays and EdU incorporation, assessing cell cycle perturbations via flow cytometry with PI staining, and analyzing histone acetylation changes at replication origins by ChIP-qPCR and western blotting for H4K5/K8/K12 and H3K14 acetylation. Differential gene expression can be profiled by RNA-seq to uncover KAT7-dependent transcriptional programs. The cells are also suited for clonogenic survival assays to measure proliferation capacity and drug response studies targeting replication stress pathways. For further information, please contact Ascent Research.
