CCDC6 Knockout A2780 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated from the A2780 human ovarian carcinoma epithelial cell line. This product provides a loss-of-function model for the tumor suppressor gene CCDC6, enabling detailed investigation of its roles in DNA damage response and apoptosis without the potential biases of clonal selection. The polyclonal format ensures a heterogeneous representation of targeted disruptive mutations, suitable for robust functional genomic studies.
The parental A2780 cell line was originally established from an untreated patient with ovarian carcinoma and is extensively characterized as an epithelial model of ovarian cancer. These cells retain genetic and phenotypic features of the tumor type, including sensitivity to platinum-based chemotherapeutic agents, making them an ideal host for examining the molecular determinants of chemoresistance and DNA repair pathways.
CCDC6 functions as a substrate recognition subunit of the DCX (DDB1-CUL4A-WDR42A) E3 ubiquitin ligase complex. Following genotoxic stress, ATM kinase phosphorylates CCDC6, triggering the ubiquitination and proteasomal degradation of HDAC1. This event relieves HDAC1-mediated transcriptional repression of pro-apoptotic genes, thereby facilitating p53 transactivation and the execution of apoptosis. CCDC6 directly interacts with DDB1, CUL4A, ATM, p53, HDAC1, CREB1, and PPP4C, forming a signaling node that links DNA damage sensors to downstream effectors including BAX, BCL2, and caspase-9. Disruption of CCDC6 abrogates this pathway, impairing DNA damage repair and apoptotic signaling, which contributes to therapeutic resistance in multiple cancer types.
In the context of A2780 ovarian carcinoma cells, the loss of CCDC6 is particularly relevant because CCDC6 alterations are frequently observed in ovarian cancer and are associated with deficient DNA damage response and resistance to platinum-based chemotherapy. This knockout model allows researchers to dissect CCDC6-dependent mechanisms of ATM/ATR signaling, homologous recombination repair, and p53-mediated cell death, providing a physiologically relevant system to study ovarian cancer progression and to identify synthetic lethal targets that may be exploited therapeutically.
Research applications for this polyclonal knockout cell population include mechanistic studies of DNA damage repair, apoptosis signaling, and chemoresistance in ovarian cancer. It is well suited for synthetic lethality screens, drug sensitivity profiling, and functional genomics experiments. Representative techniques compatible with this product include western blotting, immunofluorescence detection of ??H2AX foci, flow cytometric apoptosis assays (Annexin V/PI), cell viability assays (MTT, CellTiter-Glo), comet assay, RNA-seq, co-immunoprecipitation, and phospho-signaling analysis. For additional details, pricing, or to place an order, please contact Ascent Research.
