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Here, the authors use cryo-EM and machine-learning-based tools to analyze structurally heterogeneous ribosome assembly intermediates. They uncover a new proofreading function of the bacterial methyltransferase KsgA, wherein this assembly factor recognizes and drives partial disassembly of translationally incompetent particles, thereby affording these intermediates another opportunity to assemble in an active form.
Gangwar et al. describe the cumulative effect of the potentiating CNIH2 and inhibitory γ5 auxiliary subunits on GluA2 AMPA receptor activation and desensitization gating, polyamine block and noncompetitive inhibition by antiepileptic drug perampanel.
Here the authors describe the backbone structural dynamics of K-Ras in its active state by solution NMR. Comparing wild-type K-Ras to oncogenic mutants unveils cooperative transitions to a highly dynamic excited state that advances our understanding of the GTPase activities of K-Ras.
Using cryo-EM, Karasmanis, Reimer, and Kendrick et al. reveal a Lis1-mediated dynein dimer, termed Chi, that serves as intermediate state in relieving dynein’s autoinhibition.
Here, using structural and biochemical data, the authors provide a comprehensive overview of Okazaki fragment maturation in Escherichia coli, demonstrating a relay of events among the involved enzymes regulating an efficient four-point molecular handover.
The third variable (V3) loop on the HIV-1 Env glycoprotein is required for viral entry. Here, the authors applied DARPin technology to produce broadly neutralizing inhibitors targeting a region of V3 that becomes accessible after binding to the CD4 receptor.
Here the authors present a functional, tagged version of Rad51, which allows dynamic, in vivo studies of Rad51–ssDNA nucleoprotein filament (NPF) formation. NPFs display notable flexibility, which allows them to implement an efficient search strategy for homolog sequences amidst the crowded nucleus.
Here the authors report how cohesin loader Scc2 is recruited to chromatin during replication by the processivity-promoting factor PCNA to support de novo cohesin loading onto replicated sister DNA and ensure sister chromatid cohesion.
Here the authors show that Fanconi anemia repair proteins protect against LINE-1 retrotransposition, particularly during early development when the primary protective pathway of transcriptional silencing is inactive.
Here, using population-based modeling on ensemble Hi-C data, the authors provide an expansive overview of how the genic chromatin microenvironment influences its potential involvement in different functions, such as transcription, DNA replication, and chromatin compartmentalization. Their results unveil a key role of nuclear speckles in genome organization.
Chromosome-wide late replication is an enigmatic hallmark of the inactive X. Here, the authors combined scRepli-seq and 4C-seq to reveal its layered 3D architecture, which could explain local differences in heterochromatin stability.
Here, the authors use cryo-EM, biochemical and yeast assays of the HAT NuA4–Tip60 to reveal its mechanism of acetylating distant nucleosomes through the Epl1 linker establishing long-range chromatin interactions.
In this study, Yang et al. show that the mitochondrial-stress-induced cleavage product of DELE1 oligomerizes to generate a signaling platform that activates a cascade of kinases, triggering the integrated stress response.
Here the authors present the high-resolution structures of 17 antibiotics bound to Escherichia coli ribosomes, which may inform the development of new antibacterial agents. Their results unveil a conserved manner of antibiotic binding to the ribosome, including ordered water molecules.
To study the dynamic 3D structure of specific loci, the authors combine a computer modeling scheme based on polymer physics with experimental validation. Their results indicate that chromatin dynamics are sufficiently fast to sample all possible locus conformations within minutes, generating wide dynamic variability within single cells.
Inhibitor of apoptosis BIRC2 mediates cell death and survival. Tencer et al. report the molecular mechanism underlying BIRC2 cellular localization and describe the effect of BIRC2 inhibition on the death of cancer cells and HIV-1-infected T cells.
Here, the authors show that although transcription is severely diminished in nucleated erythrocytes, it persists at genes involved in promoter-proximal pausing of RNA polymerase II. Erythrocyte nuclei exhibit a reoriented architecture with accessible chromatin at the periphery and retain chromatin organization at minidomains surrounding RNA polymerase II-paused gene promoters.
Here, the authors show that HDAC1 and HDAC2 genetically interact, with each paralog being synthetically lethal with hemizygous deletion of the other. Mechanistically, HDAC1/2 co-deficiency leads to degradation of the NuRD complex, decreased chromatin accessibility and aberrant enhancer-based interactions.
Here, the authors identify four novel regulators of the 2-cell-like state, and thus totipotency, via unbiased CRISPR knockout screens and Dazl re-expression as a readout. They show that these factors act upstream of DPPA2 and DUX, and independently of p53.
Here, using structural and biochemical methods, the authors reveal the existence of an intermediate state of the influenza polymerase, which allows it to toggle between the transcribing and replicative states.