Targeting DNA termini with a small-molecule natural product analogue: a DNA end-binder (DEB) to augment DNA double-strand breaks.

ABSTRACT: DNA double-strand breaks generate exposed DNA ends, which, if left unrepaired, can be highly deleterious. Eukaryotic cells have evolved multiple mechanisms to safeguard these DNA ends and maintain genomic integrity. This study screened synthetic natural product analogues to identify small-molecule ligands that selectively sequester broken DNA ends. A potential DNA end-binder (DEB) was serendipitously identified among discolin and bacillimidazole-based compounds. DEB interaction resulted in fluorescence quenching of ethidium bromide in linear but not circular DNA, indicating preferential binding to DNA termini. DEB inhibited exonucleases and ligases that bind DNA termini, forming a stable complex, as confirmed by gel retardation analysis. Molecular dynamics simulations revealed strong bindi

SUBMITTER: Tuti N 

PROVIDER: S-EPMC12541385 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature