The DTX3L Knockout THP-1 Cell Line is a CRISPR/Cas9-edited knockout cell line derived from THP-1 human monocytic leukemia cells. This product features targeted disruption of DTX3L, which encodes an E3 ubiquitin ligase involved in DNA double-strand break repair and antiviral innate immunity, providing a loss-of-function model for mechanistic studies.
THP-1 is a monocytic leukemia cell line derived from an acute monocytic leukemia patient, widely used for studying monocyte/macrophage biology, innate immunity, and leukemogenesis. These cells exhibit phagocytic activity, cytokine secretion, and a TP53 mutation that alters DNA damage response pathways, making them a relevant host for investigating DNA repair and signaling in a leukemic context.
DTX3L is an E3 ubiquitin ligase that partners with PARP9 to catalyze K63-linked polyubiquitination of histone H2B, facilitating recruitment of BRCA1 and BARD1 to DNA double-strand breaks for repair by homologous recombination. DTX3L is a key interferon-stimulated gene, transcriptionally induced by interferons via JAK-STAT signaling (STAT1, STAT2, IRF9), and it enhances antiviral innate immune responses. The DTX3L-PARP9 complex interacts with ubiquitin-conjugating enzymes (UBE2D/UBCH5) and functions downstream of DNA damage kinases ATM and ATR, integrating signals from ??H2AX, MDC1, RNF8, and RNF168 to promote K63-ubiquitin-dependent BRCA1 recruitment.
In the TP53-mutant THP-1 leukemic background, DTX3L knockout disrupts DNA repair and interferon signaling, providing a model to explore synthetic lethality with PARP inhibitors. The knockout also impairs antiviral innate responses and macrophage activation, enabling studies of viral infection, phagocytosis, and cytokine secretion. This model is valuable for dissecting the crosstalk between DNA damage, ubiquitin signaling, and innate immunity in leukemia.
Researchers can use Western blotting to confirm DTX3L loss and ubiquitin levels, immunofluorescence for DNA damage foci, RT-qPCR for interferon-stimulated genes, and comet assays to quantify DNA damage. Functional assays include viral infection, phagocytosis, and cytokine ELISA, while drug sensitivity testing with PARP inhibitors facilitates synthetic lethality studies. For more information, please contact Ascent Research.
