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Here, the authors show that DYNLL1 accumulates at DNA double-strand breaks via 53BP1, where it inhibits MRE11-dependent end resection by disrupting its dimerization, and it restricts recruitment of the Shieldin complex.
Here authors present SAMOSA-ChAAT, a method for resolving how chromatin-interacting proteins restructure individual chromatin fibers, in high throughput and at scale. They provide evidence that the imitation switch family remodeling enzymes sense nucleosome density to program internucleosomal spacing on individual molecules.
Here the authors report structural and biochemical analyses of the mitochondrial TOM–TIM23 supercomplex, providing insights into how the substrates are transported through the outer and inner membranes.
Goekbuget et al. characterize the role of the developmentally essential transcriptional repressor FOXD3 in limiting transcription of highly active genes upon entry into S phase to promote faithful DNA replication and to protect genome integrity.
Mitochondrial DNA is critical for cell function, but how growing cells maintain stable concentrations is unclear. Seel et al. find that cells couple mitochondrial DNA copy number directly to cell volume through nuclear-encoded limiting factors, whose amount increases with cell volume.
Here the authors develop CRISPR–ChIP to enable the identification of factors required for chromatin regulation. Using this new method, they unveil a functional partitioning of H3K79 methylation into two distinct regulatory units, with important implications in MLL leukemia.
Capper et al. uncover how bicarbonate binds to the anion exchanger 1 (AE1), elucidate how drugs inhibit AE1 via distinct mechanisms, and generate a series of AE1 inhibitors using structure-based drug discovery.
A family of large-genome bacteriophages assembles a protective protein shell around its replicating DNA called the ‘phage nucleus’. Here, Enustun et al. use proteomics to identify a set of proteins associated with the phage nucleus that aid macromolecule transport through the nuclear shell.
The proteasome core particle (CP) assembles through the fusion of two half-CP precursors, yielding a complete but immature CP structure. Here the authors identify by cryogenic electron microscopy the structure of a post-fusion assembly intermediate, revealing how associated factors collaborate to chaperone CP assembly and maturation.
Here, the authors show that DNA-PK and TRF2, via its iDDR, suppress MRN nucleolytic processing of leading-end blunt telomeres, which are instead processed by Apollo or, in its absence, are aberrantly fused by alternative end-joining.
Using cryo-EM, the authors show that the mammalian CCR4–NOT complex specifically recognizes stalled translating ribosomes similar to the yeast complex, locks them in a translation-incompetent state and coordinates their ubiquitylation, highlighting its central role in linking translation to mRNA stability.
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.