This product consists of a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human DNAJA2 gene. The DNAJA2 Knockout HAP1 Polyclonal Cells represent a heterogeneous population of CRISPR/Cas9-edited HAP1 cells carrying targeted disruption of the endogenous DNAJA2 gene, providing a versatile loss-of-function model for functional genomics studies.
HAP1 cells are a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia line, exhibiting adherent fibroblastoid morphology and a predominantly haploid karyotype with the exception of disomy for chromosome 8. This genetic simplicity facilitates efficient gene editing and unambiguous genotype?Cphenotype correlations, making HAP1 a widely used model system in genetic research, cancer biology, and drug target validation studies.
DNAJA2 encodes a J-domain co-chaperone of the Hsp40/DnaJ family that partners with Hsp70 (including HSPA1A and HSPA8) to drive ATP hydrolysis and promote substrate binding, folding, and trafficking. DNAJA2 is integral to the Hsp70 chaperone cycle, linking it to the Hsp90 machinery through interactions with HOP/STIP1 and CHIP/STUB1, and to protein degradation pathways via the BAG family of nucleotide exchange factors. Its activity is tightly regulated by the heat shock transcription factors HSF1 and HSF2 downstream of cellular stress and PI3K/Akt signaling. Loss of DNAJA2 disrupts Hsp70-mediated protein quality control, impairing the handling of diverse client proteins including steroid hormone receptors, signaling kinases, and components of clathrin-mediated endocytosis, ultimately sensitizing cells to proteotoxic stress and agents such as cisplatin.
In the HAP1 cellular context, DNAJA2 knockout provides a clean genetic background to dissect the Hsp70 chaperone network without confounding polyploid complexity. The near-haploid state ensures that loss-of-function phenotypes are not masked by a second allele, enabling robust detection of defects in protein folding, stress granule dynamics, and ubiquitin?Cproteasome system activity. Given the role of chaperones in cancer cell survival, this model is particularly relevant for exploring mechanisms of drug resistance in leukemic cells and for screening compounds that modulate chaperone activity.
Typical applications include biochemical characterization of Hsp70?Cco-chaperone interactions via co-immunoprecipitation and proteomics, functional assays monitoring proteasome activity and protein aggregation under heat shock or MG132 treatment, and high-content imaging of stress granule formation. This knockout cell population is also suitable for genome-wide CRISPR screens, transcriptomic profiling by RNA-seq, and drug sensitivity testing to identify modulators of chaperone-mediated resistance. For further details or to discuss your specific research needs, please contact Ascent Research.
