CK2-mediated HDAC5 shuttling regulates DNA end resection through Ku70 deacetylation.

ABSTRACT: Rationale: Loss of histone deacetylase 5 (HDAC5) is frequently observed in multiple malignancies, including pancreatic ductal adenocarcinoma (PDAC), and is associated with poor patient survival. Although HDAC5 has been implicated in DNA damage repair, the molecular mechanisms by which it regulates DNA double-strand break (DSB) repair pathway choice remain unclear. Methods: Using PDAC cell lines, genetically engineered mouse models, patient-derived organoids, and biochemical assays, we investigated the role of HDAC5 in DNA end resection and homologous recombination (HR). Protein interactions, post-translational modifications, DNA repair pathway activity, and cellular responses to DNA damage and PARP inhibition were systematically analyzed. Results: We identify HDAC5 as

SUBMITTER: Liang X 

PROVIDER: S-EPMC12846757 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature