AlphaFold2 has already changed structural biology, but its true power may lie in how it changes the way we think about cells and organisms. Two studies broadly assess its utility and limitations in providing structural models to shed light in areas such as mutations, protein–protein interactions, and phosphorylation.

Craspase is newly identified type III CRISPR–Cas system with two major components: the nuclease Cas7-11, and the protease TPR-CHAT. Craspases perform a delicate balancing act between nuclease and protease activity to achieve immune tolerance and defense in bacteria, and show promise as highly regulatable genome-editing tools.

Gene transcription initiation is a highly regulated process in which Pol II and general transcription factors assemble into a pre-initiation complex. Structural studies of yeast and human initiation complexes shed light on the role of the first nucleosome flanking gene promoters in controlling the transcription machinery.

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 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.

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.