The ASCC1 Knockout HeLa Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population derived from the HeLa human cervical adenocarcinoma line, featuring disruption of the ASCC1 gene encoding the activating signal cointegrator 1 complex subunit 1. This polyclonal knockout model provides a heterogeneous pool of edited cells, enabling functional studies of ASCC1 in a physiologically relevant epithelial carcinoma background. Generated via CRISPR/Cas9-mediated gene disruption, this loss-of-function model is suitable for investigating ASCC1 roles in transcription, DNA repair, and mRNA quality control.
HeLa cells are an immortalized human cervical adenocarcinoma epithelial line containing integrated human papillomavirus 18 (HPV18) sequences, which drive constitutive expression of E6 and E7 oncoproteins that disrupt p53 and retinoblastoma tumor suppressor pathways. It offers robust growth, easy genetic manipulation, and extensive multi-omics data. The HPV18-positive status confers a cancer-relevant genomic instability that makes these cells particularly informative for studying DNA damage responses and oncogenic signaling. HeLa cells endogenously express functional retinoic acid and nuclear receptor pathways, providing a suitable platform for dissecting ASCC1-dependent transcription.
ASCC1 is a core constituent of the ASC-1 transcriptional cointegrator complex, which physically bridges ligand-bound nuclear hormone receptors RAR and RXR to the basal transcriptional machinery, thereby activating retinoic acid-responsive gene expression programs including CYP26A1 and HOX genes. ASCC1 also governs non-stop mRNA decay through its association with ASCC2, ASCC3, and TRIP4 in a ribosome-associated surveillance complex that recruits the RNA exosome to stalled translation products. Independently, ASCC1 coordinates ALKBH3-mediated removal of alkylation lesions from DNA, maintaining genomic integrity. These multi?faceted roles place ASCC1 at the intersection of transcriptional activation, post?transcriptional quality control, and DNA damage response networks.
Disruption of ASCC1 in the HeLa background provides a powerful tool for dissecting pathophysiology linked to aberrant retinoic acid signaling and DNA repair deficiencies, which are implicated in neurodevelopmental syndromes such as spinal muscular atrophy with congenital bone fractures and intellectual disability. The HPV?driven transformation of HeLa cells sensitizes them to DNA alkylation damage, making the knockout model especially valuable for evaluating ALKBH3?dependent repair mechanisms and synthetic lethality interactions. Furthermore, the loss of ASCC1?mediated non?stop decay surveillance allows investigation of ribosome?associated quality control defects that may contribute to cancer cell homeostasis and stress responses.
This ASCC1 knockout cell population supports diverse applications including quantitative assessment of retinoic acid?driven transcription by dual?luciferase reporter assays, comet assays for alkylation repair, and RNA stability assays for non?stop decay. Co?immunoprecipitation and immunofluorescence can map altered interactions within the ASC?1 complex and with ALKBH3. Chromatin immunoprecipitation (ChIP?qPCR) permits direct analysis of RAR/RXR binding at endogenous target promoters, while western blotting and RT?qPCR verify changes in downstream targets such as CYP26A1. Researchers studying nuclear receptor signaling, DNA damage response, or neurodevelopmental disease will find this model a robust platform for mechanistic studies. For additional information on product specifications and availability, please contact Ascent Research.
