The MDC1 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population featuring disruption of the MDC1 gene in the Raji B lymphocyte cell line. This polyclonal product provides a genetically heterogeneous pool of loss-of-function MDC1 variants, suitable for population-based functional assays and pooled screening approaches without clonal bias.
The Raji cell line is an EBV-positive Burkitt lymphoma model derived from an 11-year-old male. It expresses surface IgM and HLA class I molecules and is extensively used to study B-cell receptor signaling, apoptosis, and EBV-mediated oncogenesis. The transformed B-cell background offers a clinically relevant system for examining DNA repair dependencies in lymphoma.
MDC1 is a key scaffold in the DNA damage response, binding ??-H2AX at double-strand breaks via tandem BRCT domains. It interacts with ATM kinase, which phosphorylates MDC1 to promote recruitment of repair factors including 53BP1, BRCA1, and the MRN complex. MDC1 coordinates ATM/ATR checkpoint signaling, facilitating cell cycle arrest and repair through homologous recombination and non-homologous end joining. It further engages ubiquitin ligases RNF8 and RNF168 to amplify damage signals, regulating downstream effectors such as CHK2 and p53 to dictate apoptosis or survival.
In Raji cells, MDC1 disruption compromises the DDR network, impacting genomic stability and therapeutic resistance. EBV-driven lymphomas often exhibit altered DNA repair, and MDC1 loss may sensitize cells to radiation, topoisomerase inhibitors, and PARP inhibitors. This model is valuable for studying radioresistance, chemoresistance, and genomic instability relevant to B-cell malignancies and Nijmegen breakage syndrome-like disorders.
The MDC1 polyclonal knockout cells support diverse experimental workflows, including immunofluorescence analysis of ??-H2AX foci, Western blotting for MDC1 and phospho-ATM, flow cytometry for cell cycle and apoptosis, and clonogenic survival assays with DNA-damaging agents. Co-immunoprecipitation and RT-qPCR enable interrogation of MDC1 interactors and repair gene expression, while Comet assays quantify DNA damage. These cells facilitate drug sensitivity profiling and development of DDR-targeted therapies in lymphoma. For further information, contact Ascent Research.
