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Huang, Rigau and colleagues observe major changes in how DNA is organized in early germ cells before they start developing into sperm or eggs. These results show that germline removes structural ‘memory’ of DNA folding to start fresh for the next generation.
This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.
Shajahan et al. unveil a repressive genomic compartment in totipotent-like cells, shaped by Zscan4 and guided by transient Z-DNA formation. This ‘Z compartment’ may be crucial for preserving totipotency in early embryos.
Tafur et al. determined the cryo-electron microscopy structure of the SEA complex (GATOR) bound to its substrate, the EGO complex (Ragulator–Rag), and showed that its GAP activity is essential for both rapid inactivation and reactivation of TORC1.
Fang et al. reveal how a bacterial circadian clock turns genes on and off at the right times of day and use the purified proteins to drive circadian gene transcription in a test tube for days.
Scholl et al. show that PopZ forms filamentous condensates driven by its helical domain and inhibited by its disordered region. Phase-dependent conformations modulate client interactions and disruption of filamentation or condensation impairs cellular function and growth.
Nagahata, Kato and Yamada et al. provide cryo-electron microscopy structures of four phylogenetically diverse RNA-guided nucleases—HfmIscB, TbaIscB, YnpsCas9 and NbaCas9—each in complex with its guide RNA and target DNA, providing insights into CRISPR–Cas9 evolution.
Annunziato, Quan and Donckele et al. identify G3BP2 (Ras–GAP SH3 domain-binding protein 2) as a molecular glue-induced neosubstrate of the CRL4CRBN E3 ubiquitin ligase. The CRBN–glue neosurface uses a molecular surface mimicry mechanism to recruit and degrade G3BP2 in a compound-dependent manner.
Yu, Yin, Zhu, Lu and colleagues show that Acr inhibits Cas activity through a scaffold RNA interaction and further develop an RNA truncation optimization strategy to enhance editing performance.
Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.
Chen et al. show that redox signals activate ADAR1 to fix faulty RNA pieces during DNA copying, ensuring smooth replication and protecting genome stability.
Ahmad et al. show that soluble histone H4 binds at histone genes and acts as a repressor of their expression. These findings suggest that histone H4 is a sensor of ongoing DNA replication. Ongoing chromatin assembly uses up soluble H4 and relieves histone gene repression; however, once DNA replication ceases, soluble H4 accumulates and represses the histone genes.
