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Gabapentinoid drugs are widely used for pain, epilepsy and mental disorders. Chen et al. report the structure of a gabapentin-bound brain and heart calcium channel, revealing the gabapentin binding site and isoform-selective binding determinants.

Using atomic force microscopy, Pan et al. show that cyclic nucleotide-gated ion channel SthK, which can be differentially activated by cAMP and cGMP, binds both cyclic nucleotides but only cAMP can access a deep-bound state that could be essential for cAMP-dependent channel activation.

Tsirigotaki et al. unveil how adipokine Leptin induces trimerization of the Leptin receptor to form a cytokine-receptor assembly critical to body weight regulation, immunity, fertility and cancer.

Zhang et al. describe structures, diverse function and subunit-specific pharmacology of three major GluN2C- and GluN2D-incorporated NMDA receptors known to exist in the brain.

In this work, the authors show that the DREAM complex suppresses the expression of numerous DNA-repair proteins in somatic cells. Suppression of the DREAM complex, either by altering individual components in Caenorhabditis elegans or chemical inhibition in human cells and progeroid mice, results in increased resistance to various DNA-damage sources during development and aging.

The authors demonstrate that cells that are deficient in H3K9 trimethylation display more compact mitotic chromosomes decorated with aberrantly high H3S10 phosphorylation and H3K27 trimethylation. By quantitative proteomics, they show that H3K9 trimethylation is essential for mitotic bookmarking by Esrrb and thus for the maintenance of epigenetic memory during cell division.

Using cryo-EM structures, single-molecule fluorescence and electrophysiological studies, Kern et al. show how LRRC8A:C volume-regulated channels assemble into heteromers and use pore-bound lipids to block conduction in a closed state.

The RNA methyltransferase (MTase) METTL1 catalyzes N⁷-methylguanosine (m⁷G) modification at position 46 in human transfer RNAs (tRNAs). Its dysregulation drives tumorigenesis in many cancer types. Two papers now reveal the structural basis of this tRNA maturation event.

The authors perform a computational analysis of mutagenesis at non-B DNA structures formed by repetitive sequences. Having removed confounding factors, they present a landscape of mutagenesis different than previously thought, in which mechanisms such as the formation of abnormal secondary structures, polymerase slippage and occasional takeover by error-prone polymerases play an important role within, but not surrounding, the motifs.

Here the authors delineate the chromatin compaction process during human erythropoiesis, observing substantial domain disruption. Heterochromatin is highly compressed and rewired, while transcription competence is a key indicator of the selected domain maintenance.

Here, the authors show that replication protein A (RPA) tends to self-assemble into dynamic condensates, in a manner that is stimulated by ssDNA and regulated by RPA2 phosphorylation. RPA condensates are functionally important for telomere clustering and RAD52-dependent telomere maintenance.

In this Review, the authors provide a comprehensive overview of recent structural studies of the cGAS–STING complex, discussing pertinent functional and mechanistic implications.

The authors show that the assembly of the meiotic chromosome axis in worms depends on activation of the master DNA-damage response kinase ATM, which leads to destabilization of the cohesin-unloader WAPL. Similar ATM-dependent WAPL inhibition also occurs in cohesin-rich genomic regions upon DNA-damage induction.

Using the site-specific incorporation of isotopically labeled glutamines and NMR, Elena-Real et al. identified helical stability of pathogenic huntingtin exon 1 as a key feature defining the aggregation propensity that triggers Huntington’s disease.

The authors develop an EM-based method to directly visualize R-loops. Applying this method to transcription-replication conflicts in human and bacterial cells, they show that DNA:RNA hybrids accumulate primarily behind replication forks, and are linked to fork slowing and fork reversal.