LMNA-PRKDC axis enhances DNA repair and promotes chemoresistance in glioblastoma.

ABSTRACT: Glioblastoma (GBM) remains one of the deadliest primary brain tumors, with rapid recurrence and near-universal resistance to temozolomide (TMZ) limiting long-term survival. In this study, we identify a clinically actionable mechanism of resistance driven by the LMNA-PRKDC axis, which enhances DNA repair and tumor cell survival following TMZ treatment. Using patient-derived xenograft models of recurrent GBM, we demonstrate that resistant tumors exhibit elevated LMNA expression and increased physical interaction with PRKDC, a central regulator of non-homologous end joining (NHEJ). This interaction accelerates the repair of TMZ-induced DNA lesions, contributing to therapeutic failure. Proteomic profiling and targeted immunoprecipitation revealed a distinct LMNA-PRKDC-associated DNA repair com

SUBMITTER: Saathoff MR 

PROVIDER: S-EPMC12811359 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature