Senataxin (SETX) prevents Myc-induced replicative stress [DRIP-seq]

ABSTRACT: Here we investigated the RNA helicase Senataxin (SETX), an enzyme that resolve RNA-DNA hybrids and R-loops, to address its role in preventing replicative stress by oncogenic Myc. Silencing of SETX led to selective engagement of the DNA damage response (DDR) upon Myc activation, leading to a robust cytotoxicity. Pharmacological dissection of the upstream kinases regulating the DDR revealed a protective role of the ATR pathway, that once inactivated, boosted SETX driven-DDR. While loss of SETX did not lead to a genome-wide increase of R-loops, mechanistic analyses revealed enhanced R-loops localized at DDR-foci and newly replicated genomic loci, compatible with a selective role of SETX in resolving RNA-DNA hybrids to alleviate Myc-induced RS.

ORGANISM(S): Homo sapiens

PROVIDER: GSE275923 | GEO | 2025/03/19

REPOSITORIES: GEO