The BRD8 Knockout Ca Ski Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Ca Ski human cervical carcinoma cell line, designed for targeted disruption of the BRD8 gene. This polyclonal pool provides a heterogeneous loss-of-function model suitable for studying BRD8-dependent biological processes without clonal selection, thereby mitigating clone-specific artifacts.
Ca Ski cells are a widely used model of HPV16-positive cervical carcinoma, originally isolated from a small intestine metastasis of a cervical adenocarcinoma. These cells express the HPV16 E6 and E7 oncoproteins, which inactivate tumor suppressors p53 and pRb, respectively, leading to deregulated cell cycle progression and genomic instability. The Ca Ski line is therefore particularly relevant for dissecting p53-dependent pathways and DNA damage responses in the context of viral oncogenesis.
BRD8 functions as a core subunit of the NuA4/TIP60 histone acetyltransferase complex, where it acts as a transcriptional co-activator by facilitating acetylation of histones H4 and H2A at target promoters. BRD8 is activated by ATM/ATR kinase signaling and directly interacts with p53, TRRAP, TIP60 (KAT5), and EP400 to drive expression of critical downstream effectors such as CDKN1A (p21) and BBC3 (PUMA). Through these interactions, BRD8 couples DNA damage sensing to chromatin remodeling, promoting p53-dependent cell cycle arrest and apoptosis.
In the Ca Ski cellular environment, where p53 function is constitutively attenuated by HPV16 E6-mediated degradation, BRD8 knockout provides a unique platform to dissect residual p53 activity and p53-independent functions of the NuA4/TIP60 complex. This model is particularly valuable for investigating chromatin-mediated mechanisms of tumor suppression and DNA repair in cervical carcinoma, as well as for assessing synthetic lethal interactions that may arise from combined p53 pathway impairment and BRD8 loss.
Researchers can employ these BRD8 knockout polyclonal cells in a range of assays, including quantitative ChIP-qPCR to assess histone H4/H2A acetylation dynamics, co-immunoprecipitation to analyze NuA4 complex integrity, and flow cytometry-based apoptosis and cell cycle profiling. This knockout model is also suited for functional studies of DNA damage signaling, TGF-??-mediated growth control, and high-throughput bromodomain inhibitor screening. For additional details or order inquiries, please contact Ascent Research.
