3D genome organization shapes DNA damage susceptibility to platinum-based drugs.

ABSTRACT: Platinum (Pt) drugs are widely utilized in cancer chemotherapy. Although cytotoxic and resistance mechanisms of Pt drugs have been thoroughly explored, it remains elusive what factors affect the receptiveness of DNA to drug-induced damage in nuclei. Here, we demonstrate that nuclear locations of chromatin play a key role in Pt drug-induced DNA damage susceptibility in vivo. By integrating data from damage-seq experiments with 3D genome structure information, we show that nuclear locations of chromatin relative to specific nuclear bodies and compartments explain patterns of cisplatin DNA damage susceptibility. This aligns with observations of cisplatin enrichment in biomolecular condensates at certain nuclear bodies. Finally, 3D structure mapping of DNA damage reveals characteristic differe

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12117463 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature