The BRCC3 Knockout Jurkat Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the BRCC3 gene has been disrupted in the Jurkat immortalized human T lymphocyte leukemia cell line. This polyclonal knockout model provides a heterogeneous pool of cells carrying diverse loss-of-function mutations, enabling robust assessment of BRCC3-dependent phenotypes without the constraints of single-cell clonal selection. The product is designed for researchers investigating the cellular roles of BRCC3 in DNA repair, cell cycle regulation, and cancer biology.
The Jurkat cell line is an extensively characterized model of human T lymphocyte biology, derived from an acute T cell leukemia. These suspension cells exhibit activated T cell signaling properties and are widely employed in studies of immune response, T cell receptor signaling, and hematological malignancies. The Jurkat background offers a well-defined genetic and biochemical context for interrogating the functions of DNA damage response genes, including those involved in maintaining genomic stability in lymphoid cells.
BRCC3 encodes a Lys-63-specific deubiquitinase that functions as a core component of the BRCA1-A complex, which also includes RAP80, Abraxas, MERIT40, and BABAM1. Following DNA double-strand breaks, the ATM kinase phosphorylates H2AX, initiating a signaling cascade that involves the ubiquitin ligases RNF8 and RNF168. BRCC3 is recruited to damage sites and removes Lys-63-linked ubiquitin chains from histone H2A and H2AX, facilitating the stable accumulation of BRCA1 and the formation of repair foci. BRCC3 thereby acts downstream of ATM and RNF8/RNF168 and upstream of BRCA1 and RAP80, regulating the choice between DNA repair pathways and cell cycle checkpoint activation. Its deubiquitinase activity is essential for proper homologous recombination repair and checkpoint maintenance.
Disruption of BRCC3 in Jurkat cells compromises the integrity of the BRCA1-A complex, leading to impaired DNA double-strand break repair and altered cell cycle checkpoint signaling. This loss-of-function model provides a valuable system for studying the consequences of defective deubiquitination in a lymphoid cellular environment. Because Jurkat cells are derived from a leukemia background, the BRCC3 knockout model is particularly suited for investigating how genomic instability contributes to cancer predisposition and for exploring synthetic lethal interactions that may be exploited therapeutically in hematological malignancies.
This polyclonal knockout cell pool is ideal for a variety of research applications, including mechanistic studies of DNA damage response using ??-H2AX immunofluorescence or comet assays, PARP inhibitor sensitivity screening, clonogenic survival assays following genotoxic stress, and co-immunoprecipitation to analyze BRCA1-A complex assembly. Additionally, it supports cell cycle profiling by flow cytometry and RAD51 foci formation assays to evaluate homologous recombination efficiency. Researchers can employ these cells to dissect Ub-dependent signaling networks and to screen for modulators of DNA repair. For additional information or to inquire about custom cell solutions, please contact Ascent Research.
