Disruption of RNA Splicing Increases Vulnerability of Cells to DNA-PK Inhibitors.

ABSTRACT: DNA-dependent protein kinase (DNA-PK) is a key effector of non-homologous end joining (NHEJ)-mediated double-strand break (DSB) repair. Since its identification, a substantial body of evidence has demonstrated that DNA-PK is frequently overexpressed in cancer, plays a critical role in tumor development and progression, and is associated with poor prognosis in cancer patients. Recent studies have also uncovered novel functions of DNA-PK, shifting the paradigm of the role of DNA-PK in oncogenesis and renewing interest in targeting DNA-PK for cancer therapy. To gain genetic insight into the cellular pathways requiring DNA-PK activity, we used a CRISPR/Cas9 screen to identify genes in which defects cause hypersensitivity to DNA-PK inhibitors. We identified over one hundred genes involved in DN

SUBMITTER: Kovina AP 

PROVIDER: S-EPMC11546466 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature