SRSF2 overexpression induces transcription-/replication-dependent DNA double-strand breaks and interferes with DNA repair pathways to promote lung tumor progression.

ABSTRACT: SRSF2 (serine/arginine-rich splicing factor 2) is a critical regulator of pre-messenger RNA splicing, which also plays noncanonical functions in transcription initiation and elongation. Although elevated levels of SRSF2 are associated with advanced stages of lung adenocarcinoma (LUAD), the mechanisms connecting SRSF2 to lung tumor progression remain unknown. We show that SRSF2 overexpression increases global transcription and replicative stress in LUAD cells, which correlates with the production of DNA damage, notably double-strand breaks (DSBs), likely resulting from conflicts between transcription and replication. Moreover, SRSF2 regulates DNA repair pathways by promoting homologous recombination and inhibiting nonhomologous end joining. Mechanistically, SRSF2 interacts with and enhances

SUBMITTER: Khalife M 

PROVIDER: S-EPMC11963763 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature