Subcellular fractionation of Drosophila S2 cells upon foldamer treatment

ABSTRACT: The use of synthetic chemicals to selectively interfere with chromatin and the chromatin-bound proteome represents a great opportunity for pharmacological intervention. Recently, synthetic foldamers that mimic the charge surface of double-stranded DNA have been shown to interfere with selected protein-DNA interactions. However, to better understand their pharmacological potential and to improve their specificity and selectivity their effect on complex chromatin needs to be investigated. We therefore systematically studied the influence of these DNA-mimicking foldamers on the chromatin-bound bound proteome using an in vitro chromatin assembly extract. Our studies revealed an efficient interference with the chromatin-associated origin recognition complex that plays an important role in initiating eukaryotic chromatin replication. This interference is mediated by a strong direct interaction between the foldamers and the origin recognition complex and has an effect in tissue culture cells where the addition of foldamer led to an S-phase arrest. Foldamers that mimic double-stranded nucleic acids thus emerge as a powerful tool with designable features to alter chromatin assembly and selectively interfere with biological mechanisms.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

SUBMITTER: Ignasi Forne  

LAB HEAD: Prof. Dr. Axel Imhof

PROVIDER: PXD042288 | Pride | 2023-09-04

REPOSITORIES: Pride