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DNA2 suppresses recombination-restarted replication and checkpoint activation at stalled forks, and its loss triggers recombination-dependent synthesis, checkpoint signalling and cell-cycle exit, highlighting its essential role in proliferation and growth failure in primordial dwarfism.

Intraepithelial lymphocytes (IEL) respond to IL-15 complexed with IL-15Ra but how this intrinsically affects IEL is unclear. Here the authors use proteomics analyses of the main mouse IEL subsets and identify PIM kinases as essential for IEL proliferation, metabolism and effector function downstream of IL-15.

What underlies the synthetic lethality between BRCA1/2 or 53BP1 loss and Polθ loss is unclear. Here, the authors show that RPA-RAD52-MRE11 drive lethality when Polθ is absent in these cells. In BRCA1/2-deficient cells, sensitivity to Polθ inhibition additionally depends on the inhibited protein.

Myelinating cells differentially myelinate axons of different diameters, however whether they can also restrict radial axonal growth remained unclear. Here, the authors show that CMTM6 in Schwann cells restricts axon diameters, affecting sensory nerve conduction and behavioral performance.

Chemical inducer of dimerization (CID) modules can be used to effectively control biological processes; however, CID modules have been explored primarily in engineering cells for in vitro applications using inducers that have limited clinical utility. Here, the authors identify a CID module with favorable properties to enable rapid translation from in vitro applications to potential use in humans.

BRCA1–BARD1 has a role in replication fork protection that is mediated by a mechanism of phosphorylation-targeted isomerization of BRCA1 and is independent of the canonical interaction between BRCA1 and PALB2.

Weyl semimetals exhibit exotic properties owing to the presence of Weyl fermions. Here, Xu et al. show that tantalum phosphide is an ideal platform for studying the transport properties of these particles because its low-energy properties are dominated by a single type of Weyl fermion.

Transition metal oxides serve as important electrocatalysts for the oxygen evolution reaction, although Co-based oxides typically undergo pH-dependent dynamic surface reconstruction under catalytic conditions. Now the correlations between Co redox dynamics, flat band potential and Co oxidation state changes have been established to explain the pH dependency of oxygen evolution activity.

Xist RNA is the master regulator of X chromosome inactivation. Here the authors describe a systematic analysis of Xist-mediated allelic silencing in mouse ESC models and define the contribution of different pathways that regulate gene silencing.

Brain morphology is complex, heterogenous and miniaturized—and notoriously difficult to visualize. Dembitskaya et al. show how fluorescence ‘shadow imaging’ gives detailed and comprehensive access to the cellular architecture of the mouse brain in vivo.

Water thermodynamics drive changes in macromolecular assembly that rapidly restore intracellular water availability in response to physiological fluctuations in temperature, pressure and osmotic strength.

CMTM6 maintains PD-L1 at the plasma membrane by inhibiting its lysosome-mediated degradation and promoting its recycling.

In the study, the authors identify a protein excreted by the parasite Trichuris muris, p43, which can modulate IL-13 function, a key cytokine involved in host protection. These data suggest that p43 may be a novel therapeutic target for both whipworm infections and IL13 mediated pathologies.

Osmotic compensation by electroneutral ion transport buffers TORC1-mediated changes in the cytosolic proteome, and maintains intracellular homeostasis and cell volume over the circadian cycle. Here, the authors find such ion content changes drive daily rhythms in cardiomyocyte electrical activity.

Poly(ADP-ribose)-polymerases (PARPs) are a cornerstone of the DNA damage response that promote DNA repair by modifying target proteins with ADP-ribose. Here, the authors show serine ADP-ribosylation of the H3 variant H3b maintains genome stability by coupling DNA repair with mitotic entry in Dictyostelium by regulating double strand break repair by nonhomologous end-joining (NHEJ).

In fibrotic biliary disease, portal fibroblasts promote both biliary scarring and bile duct regeneration. Here, the authors report that the non-canonical Wnt-PCP signalling promotes bile duct scarring in mice, and inhibition of Wnt-ligands reduces the scarring without impairing regeneration.

Bourdon et al. demonstrate the possibility to ectopically synthesize callose, a polymer restricted to primary cell walls, into Arabidopsis and aspen secondary cell walls to manipulate their ultrastructure and ultimately reduce their recalcitrance.

Detailed knowledge of the low-energy electronic structure is required to understand the Mott insulating phase of Ca₂RuO₄. Here, Sutter et al. provide directly the experimental band structure of the paramagnetic insulating phase of Ca₂RuO₄and unveil the electronic origin of its Mott phase.

Th17 cells are critical players in the immunopathology of a range of autoimmune diseases. Here the authors implicate Hedgehog signaling in Th17 polarization and in the immunopathology of intestinal inflammation in murine models and suggest therapeutic targeting of Hedgehog signaling in the context of inflammatory bowel disease.

The mechanism by which ingested material accesses the cytosol for cross-presentation is unclear. Caetano Reis e Sousa and colleagues demonstrate that signaling via the lectin receptor DNGR-1 ruptures the phagosome and releases its contents to the cytosol for cross-presentation.

Structural insights demonstrating small-molecule-mediated dimerization of BRD4 bromodomains led to the development of biBET, a compound that potently inhibits BRD4–acetyl-lysine interactions by bivalent binding to tandem bromodomains.

Magnons are excitations of magnetic materials that can have topological properties similar to those of electrons. Here, the authors show that the magnons of the bulk ferromagnet Mn₅Ge₃ are topological and can be controlled with a magnetic field.

Ralstonia solanacearum evades plant immunity by producing an atypical flagellin protein, thus causing bacterial wilt disease. Here, Wei et al. show that soybean has evolved a divergent flagellin receptor that recognises R. solanacearum flagellin and enhances wilt resistance when transferred to other plants.

In this Review, Henry and DeGregori discuss the contributions of the various models and methods used to study the connection between ageing and cancer, highlighting the strengths and limitations of those models and technologies, as well as advocating for the wider adoption of age-appropriate models of cancer to improve our clinical translation of approaches to prevent and treat human cancers.

Defective ribonucleotide excision repair causes ID4, an indel cancer signature characterized by deletions of 2–5 base pairs.