PARG Governs a PARylation-Ubiquitination Toggle that Stabilizes RAD51AP1 to Drive Homologous Recombination-Mediated Chemoresistance.
- Open access
PARG stabilizes RAD51AP1 through a PARylation-ubiquitination switch, promoting homologous recombination repair and contributing to chemoresistance in gastric cancer.
- Why it matters: Gastric cancer has limited targeted treatments, especially for HER2-negative cases, and understanding mechanisms of chemoresistance is crucial for improving therapy outcomes.
- What they did: The study used bioinformatics, drug screening, and patient-derived models to show that PARG binds and dePARylates RAD51AP1, preventing its degradation and enhancing DNA repair, with high PARG and RAD51AP1 levels linked to poor prognosis.
- The result: Inhibiting PARG destabilizes RAD51AP1, increases sensitivity to fluoropyrimidines like 5-FU, and improves treatment efficacy, suggesting the PARG-RAD51AP1 axis as a promising therapeutic target and biomarker in gastric cancer.