MSH3 Knockout Raji Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human Raji B lymphocyte line, featuring targeted disruption of the MSH3 gene. This model provides a stable loss-of-function system for investigating DNA mismatch repair (MMR) mechanisms, microsatellite stability, and associated genomic maintenance processes. The polyclonal nature ensures a heterogeneous yet consistently MSH3-deficient background, suitable for pooled functional assays without the need for single-cell clonal isolation, making it an accessible tool for studying MMR-related pathways in a relevant cellular context.
The Raji host cell line originates from a Burkitt lymphoma patient and is characterized as an Epstein-Barr virus (EBV)-positive lymphoblastoid cell line. As B lymphocytes, Raji cells are mediators of humoral immunity, engaging in antibody production and antigen presentation. Their rapid proliferation and transformed state make them a robust model for cancer genetics and DNA repair research. The EBV-positive status further allows investigation of viral interactions with host DNA damage response pathways, adding a dimension relevant to oncogenic mechanisms and immunology.
MSH3 forms the MutS?? mismatch recognition complex with MSH2, specifically binding to insertion/deletion loops that arise during DNA replication. Upon lesion recognition, MutS?? recruits downstream MMR components including the MLH1/PMS2 endonuclease heterodimer, exonuclease EXO1, proliferating cell nuclear antigen (PCNA), replication protein A (RPA), replication factor C (RFC), and DNA ligase I. These factors coordinate error excision and repair synthesis to maintain microsatellite stability. MSH3 function is regulated by upstream DNA damage signals, cell cycle regulators such as cyclins, and p53-mediated checkpoint pathways. Disruption of MSH3 leads to an accumulation of insertion/deletion mutations, compromising genomic integrity and promoting tumorigenesis.
In the Raji B lymphocyte background, MSH3 knockout recapitulates MMR deficiency observed in Lynch syndrome and sporadic microsatellite instability-positive cancers such as colorectal and endometrial carcinomas. This lymphoblastoid model allows researchers to dissect the specific contribution of MutS??-dependent repair defects to lymphomagenesis and immune cell dysfunction. It also facilitates the study of compensatory pathways activated upon MMR loss and enables assessment of synthetic lethal interactions, particularly with poly(ADP-ribose) polymerase (PARP) inhibitors, which have shown promise in MMR-deficient tumors.
This polyclonal knockout cell population supports a range of assays including mismatch repair activity measurements, microsatellite instability testing, Western blot analysis of MMR components (MSH2, MLH1, PMS2), and drug sensitivity profiling with genotoxic agents like cisplatin and PARP inhibitors. Additional applications encompass colony formation assays to evaluate genetic stability, cell cycle analysis under DNA damage conditions, and synthetic lethality screens. The model is also suitable for studying DNA damage response kinetics and exploring resistance mechanisms to chemotherapeutics. For further details on product availability and specifications, please contact Ascent Research.
