The APEX1 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-mediated gene-disrupted polyclonal cell population targeting human APEX1 in the HAP1 cell line. This loss-of-function model enables investigation of APEX1-dependent pathways in a controlled in vitro system.
HAP1 cells are a near-haploid human cell line derived from the KBM-7 chronic myelogenous leukemia (CML) line, originating from a male donor. Their near-haploid karyotype simplifies genetic analysis, making them especially suitable for knockout studies. These hematopoietic progenitor cells retain characteristics of myeloid leukemia, providing a relevant model for hematological malignancy research.
APEX1 encodes a dual-function protein: an apurinic/apyrimidinic (AP) endonuclease in base excision repair (BER) that cleaves abasic sites, and a redox factor that maintains transcription factors in a reduced, active state. In BER, it interacts with XRCC1, POLB, and PCNA to coordinate repair of oxidative lesions. Its redox function activates transcription factors HIF1A, TP53, RELA (NF-??B), JUN (AP-1), and STAT3, which govern genes for survival, proliferation, and inflammation. APEX1 is regulated by reactive oxygen species (ROS), HIF1A, TP53, NFE2L2 (NRF2), and CSNK2A1 (CK2), and acts upstream of AP-1, NF-??B, HIF1A, TP53, and STAT3 transcriptional programs. It also partners with TXN and NPM1 in redox signaling and nucleolar functions, linking oxidative stress to gene expression control.
In the HAP1 CML background, APEX1 disruption dissects the intersection of DNA repair and redox-regulated transcription in a leukemia-relevant context. APEX1 overexpression is linked to chemoresistance, and its BER activity protects against oxidative DNA damage. The near-haploid genome minimizes allelic variability, clarifying APEX1-dependent phenotypes. This model is valuable for studying how APEX1 loss alters NF-??B and AP-1 activity, relevant to cancer and inflammatory diseases, and enables exploration of synthetic lethal interactions for therapeutic targeting.
This polyclonal knockout pool supports various assays: Western blotting, AP endonuclease activity measurements, redox EMSA, cell viability under oxidative stress, immunofluorescence, RNA-seq, co-immunoprecipitation, and drug sensitivity profiling. Applications include functional genomics of DNA repair, redox transcriptional regulation, cancer drug resistance, oxidative stress response research, and target validation for APEX1 inhibitors. Combination studies with DNA-damaging chemotherapeutics or redox-modulating agents are particularly informative. For further information, contact Ascent Research.
