New work on DNA polymerase λ highlights its remarkable flexibility. This fits with the generally adaptable nature of the DNA-repair process in which this enzyme is involved—nonhomologous end-joining—which allows this mechanism to handle diverse types of broken DNA ends in order to restore the duplex structure, albeit with a loss of information at the join.

Nuclear actin polymerization helps facilitate chromosome compartment switches that can shift damaged DNA toward a nuclear environment that is favorable for DNA repair. Yet shifting multiple broken DNA strands together can also increase the likelihood of misjoining of the DNA ends and subsequent formation of translocations.

In this Perspective the authors discuss the major challenges when studying the role of enhancers in disease etiology, highlighting a path forward for future studies aiming to understand the molecular basis of enhanceropathies.

Cryo-EM of human PRPS1 shows the nucleotide-synthesizing enzyme assembling into filaments that accommodate active and inhibited conformations. Engineered and disease mutations reveal that filament assembly stabilizes allosteric sites, enhancing catalytic activity.

Tan et al. found that topoisomerase-independent DNA nicking is required for most, if not all, signal-induced acute enhancer activation programs, nucleating formation of a Ku70–HP1γ–Med26 complex required to facilitate transcriptional activation.

Postel et al. have determined a multidomain structure of GR in complex with ligand, DNA and a co-regulator peptide that demonstrates how GR forms a distinct architecture on DNA and how signal transmission can be modulated by the ligand pharmacophore.

Determination of the high-resolution structure of yeast TORC1 allows characterization of the precise interfaces of interaction between inactive TORC1 and TORC1′ polymers and identification of the mode of binding of active EGOC on TORC1.

Here the authors explore the ability of AlphaFold2 to predict structures across the human protein-protein interactome and the limitations thereof.

Comprehensive poly(A)-inclusive RNA isoform sequencing throughout the human oocyte and preimplantation embryo development reveals poly(A)-tail-mediated maternal mRNA remodeling that is essential for human embryo development.