Major Finding: PARP inhibition induces eviction of histones, and the chaperone NASP is required to recycle these histones to prevent DNA damage and promote resistance. Concept: Histone recycling repre...

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

Marin et al. report the role of lamin proteins and the lamin B receptor (LBR) in chromatin positioning at the nuclear periphery. Knockout of all lamins and LBR in mouse embryonic stem cells leads to h...

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

Nature Reviews Genetics, Published online: 16 June 2025; doi:10.1038/s41576-025-00866-7Hakhamanesh Mostafavi recalls a landmark paper by Boyle et al. on the omnigenic model, which proposed that complex traits are influenced by thousands of genes across the genome, including many that are only indirectly related to a trait through regulatory networks.

G-quadruplexes (G4s) are prevalent DNA structures that regulate transcription but also threaten genome stability. How G4 dynamics are controlled remains poorly understood. Here, we report that RNA tra...

Acquired therapeutic resistance is a key contributor to cancer treatment failure, requiring new approaches to address its complex mechanisms. In this Roadmap, Soragni, Knudsen and colleagues discuss the mechanisms of acquired resistance and the models to better study it. Finally, they promote integration of biomarker-driven strategies and cutting-edge technologies to advance predictive and proactive prevention in cancer therapy.