Zhu, Fu, Zhu, Li and colleagues found that the key DNA repair enzyme poly(ADP-ribose) polymerase 1 promotes transcriptional restart after DNA damage through PARylating and stabilizing AFF1 by preventing its ubiquitylation by the E3 ligase Siah1.

This study presents prime-editing-based inversion with enhanced performance, a prime editing-based system that enables efficient and precise genomic inversions from kilobase to chromosome scale, offering a powerful tool for chromosomal engineering, disease modeling and studying three-dimensional genome architecture.

In plants, oxidosqualene cyclases (OSCs) perform a highly complex single reaction to generate the basis of all triterpenoid diversity. Here the authors leverage genome mining and transient expression to uncover multiple evolutionary and mechanistic insights for OSCs across the plant kingdom.

This Review explores how post-translational modifications orchestrate replication stress responses by regulating checkpoint signaling, DNA repair and fork remodeling, thereby preserving genome stability under genotoxic conditions.

Engineered aminoacyl-tRNA synthetase (aaRS) mutants have been developed that facilitate ultrafast bioorthogonal noncanonical amino acid tagging (BONCAT) of newly synthesized proteins in diverse bacteria, including ESKAPE pathogens. The substrate polyspecificity of the aaRS mutants enables pulse-chase BONCAT and differential tagging of temporally distinct nascent proteomes in cells.

Low-antigen-expressing cancers are a challenge to existing chimeric antigen receptor (CAR)-T cell-based therapies. Now, it has been shown that fusion of intrinsically disordered regions to CARs induces CAR condensation and enhances antigen sensitivity and killing activity of CAR-T cells.

Static protein structures can capture the association of lipids, but it is unclear whether the association is due to lipids acting as long-lived ligands or the solvation of preferred lipids around the protein. A computational-experimental framework has now shown that for the protein CLC-ec1, it is the change in lipid solvation energies that drives dimerization, with preferred lipids around the protein modulating this driving force.

The development of soluble Notch agonists is a challenge because of the mechanical forces needed to activate Notch receptors. Here, bispecific Notch agonist proteins were designed that ‘pull’ on and activate Notch receptors in the presence of desired biomarkers.

Smargon et al. show that small nuclear RNAs can improve the cellular safety and efficacy of endogenous protein-mediated RNA base editing, enhancing nuclear RNA editing and the rescue of premature term...

An approach combining bioorthogonal chemistry with genetically encoded fluorogen-activating proteins enables subcellular imaging of phospholipids and glycans, as well as the visualization of lipid tra...

Inhibition of ELOVL6, a fatty acid elongation enzyme, selectively degrades mutant KRAS, disrupts its membrane localization and suppresses tumor growth, revealing a novel vulnerability in KRAS-driven c...

Designer box H/ACA RNA-guided pseudouridylation can target both mRNA and tRNA. Modifying the first U of a stop codon and U36 of the matching anticodon forms one Ψ–Ψ and two Watson–Crick pairs, enablin...

The use of bulky protein tags and the limited positions available for probe introduction restrict current methods for studying protein microenvironments at high spatial resolution. Here the authors genetically incorporate small environment-sensitive fluorescent amino acids to visualize real-time microenvironmental changes at specific protein substructures.

Using computational and experimental methods, Ouyang and Chen et al. reveal a drug design principle that the hydrophobic properties of small-molecule drugs significantly influence their ability to eng...

Many animals display brilliant colors thanks to the precise formation of guanine crystals within specialized organelles. Here, the authors demonstrate that dynamic pH shifts orchestrate this process: ...

The signal transducer and activator of transcription (STAT) family proteins are attractive drug targets but tools to monitor their activation are lacking. Now, STAT biosensors have been developed for ...

Small peptide tags (like ALFA) cause minimal disruption of proteins, but they typically lack fluorescence, which would enable knockin screening. Now, antigen-stabilizing fluorescent protein-fused nano...

This work demonstrates how a biphenyl-like scaffold targets RNA through a common base displacement mechanism by optimizing π-stacking interactions within the binding pocket, helping to inform the desi...

Recent advances in engineering bottom-up synthetic cells have created powerful compartmentalized biochemical reactors with cell-like abilities. To push the boundaries of the collective capabilities of...

Dextran sulfate sodium is a colitis inducer that stimulates a ROS–Src–IP6K2 signaling axis to generate 5-IP7, which sterically inhibits PI(4,5)P2 phosphatases to promote PI(4,5)P2-mediated E-cadherin ...

Arginylation is a post-translational modification that is difficult to distinguish from arginine residues using mass spectrometry. Now a method has been developed to profile protein arginylation ex vi...

Synthetic receptors are a powerful approach for engineering cell-based therapies that can sense and respond to their environment. Here cytokine receptor domains have been repurposed to develop enginee...

KLHL23 and RhoGDI compete for CDC42’s switch II region in a GTP- or GDP-dependent manner, driving spatiotemporal inactivation through degradation or sequestration. This dynamic control maintains membr...