PARP inhibition leads to synthetic lethality with key splicing-factor mutations in myelodysplastic syndromes.

ABSTRACT:

Background

Splicing factors are frequently mutated in patients with myelodysplastic syndromes and acute myeloid leukaemia. Recent studies have revealed convergent molecular defects caused by splicing factor mutations, among which R-loop dysregulation and resultant genome instability are suggested as contributing factors to disease progression. On the other hand, understanding how mutant cells survive upon aberrant R-loop formation and genome instability is essential for developing novel therapeutics.

Methods

The immunoprecipitation was performed to identify R-loops in association with PARP1/poly-ADP-ribosylation. The western blot, immunofluorescence, and flow cytometry assays were used to test the cell viability, cell cycle arrest, apoptosis, and ATM activation in mutant cel

SUBMITTER: Zhang F 

PROVIDER: S-EPMC11263539 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature