Two recent studies provide structural insights into how human DNA polymerase ε (Pol ε) interacts with PCNA to form a processive holoenzyme on the leading strand. A series of cryo-EM images offer structural information on the proofreading process, showing how DNA is transferred between the polymerase and exonuclease sites in human Pol ε.

An understudied subset of NOD-like receptors are involved in the reproductive system, and their dysfunction can cause infertility. The recently obtained structures of the core subcortical maternal complex assembled around one of them, NLRP5, provide important insight into this building block of early embryo cytoplasmic lattices.

Two recent studies provide mechanistic insights into how LIN28A controls changes in cell fate identity, focusing on either a let-7-independent or let-7-dependent pathway of action involving LIN28A.

Here, the authors examine and discuss the functional complexity and cellular implications of X–Y pairs, homologous genes expressed in the human sex chromosomes.

The authors here show that chromatin interactions during mouse fetal development are spatiotemporally dynamic. Integrating interactomes with other datasets predicts target genes for candidate enhancers and helps interpret noncoding risk variants in the human genome.

Here, the authors describe a noncoding genetic variant in GBA1 specific to people of African ancestry that increases the risk of neurodegenerative diseases by interfering with the splicing of mRNA, resulting in lowered protein levels and activity.

Xue et al. visualize how the antibiotic chloramphenicol reshapes the translation landscape and induces ribosome collision in bacterial cells, illuminating its context-dependent action across atomic, molecular and cellular scales.

The cryo-electron microscopy structures of γ-secretase bound to five anticancer clinical compounds reveal characteristic differences in recognition and suggest strategies for improved drug design.

The authors show cryo-electron microscopy structures of the human high-affinity sodium–dicarboxylate cotransporter, responsible for dicarboxylate import into the cell, in complex with various substrates and in different states establish the basis of substrate recognition, differentiation and release, as well as regulation of transport domain movement.

Here, the authors demonstrate how Mrs2, critical for import of Mg²⁺ into the mitochondria, transitions from open and closed five-fold symmetric states to control the influx of Mg²⁺ using an auto-ligand-gating regulation mechanism.

As 2024 closes, we take this opportunity to reflect on the highlights of our 30th anniversary year and consider what the future holds for the field.