MDS/AML-associated DDX41 helicase facilitates homologous recombination repair by potentially resolving R-loops - PubMed
a day ago
- #R-loops
- #Homologous Recombination
- #DDX41
- DDX41 mutations are linked to myeloid neoplasms like MDS and AML, with R525H being the most common missense mutation.
- DDX41 knockout cells show sensitivity to DNA-damaging agents and increased genomic instability, including more DNA double-strand breaks and R-loops.
- Wild-type DDX41 resolves R-loops in vitro, but the R525H mutant fails to do so, leading to higher R-loop accumulation and DNA damage sensitivity.
- DDX41 colocalizes with DSB marker γH2AX and R-loop marker S9.6, suggesting its role in homologous recombination (HR) repair.
- DDX41 deficiency or R525H mutation results in defective HR repair, marked by prolonged RPA foci and reduced RAD51 filament assembly.
- The study suggests DDX41 resolves R-loops to facilitate HR repair, and its dysfunction may contribute to MDS/AML pathogenesis.