Reviews & Analysis

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  • A study published in Nature Structural & Molecular Biology now unveils, at the atomic level, the initial mechanisms of prion toxicity, providing insights into the pathogenic mechanisms of a protein neurodegenerative disease caused by protein misfolding.

    • Jesús R. Requena
    News & Views
  • CST is both an ssDNA-binding complex and a DNA Pol-α/primase cofactor that coordinates the switch from G-strand elongation to C-strand fill-in during telomere maintenance. Four papers in Nature Structural & Molecular Biology and Nature provide transformative insights into CST activity, providing a platform to understand lagging-strand synthesis genome wide.

    • Conner L. Olson
    • Alexandra T. Barbour
    • Deborah S. Wuttke
    News & Views
  • Amplification of oncogene expression through extrachromosomal DNA is a common feature of many cancers and is associated with poor outcomes. Hung et al. review how regulation of extrachromosomal DNA gene expression is linked to alterations in chromatin structure and changes in contacts with DNA regulatory elements.

    • King L. Hung
    • Paul S. Mischel
    • Howard Y. Chang
    Review Article
  • Structural maintenance of chromosomes (SMC) complexes such as condensin regulate chromosome organization by extruding loops. A new study uses single-molecule imaging of condensin on supercoiled DNA to understand how condensins navigate the under- and overwound DNA states common throughout the genome.

    • Domenic N. Narducci
    • Anders S. Hansen
    News & Views
  • Two new papers describe the successful purification of the partially intact human native red blood cell band 3 multiprotein membrane complexes, providing information that the authors then use to capture the structures and interactions of multiple erythrocyte proteins using high-resolution cryo-EM.

    • Ashley M. Toye
    News & Views
  • MFSD2A mediates uptake of the essential fatty acid DHA across the blood–brain barrier. Separately, via interactions with syncytin-2, MFSD2A contributes to the formation of the mother–fetus placental boundary. Cryo-EM analysis of a human MFSD2A–syncytin-2 complex provides new insights into how MFSD2A performs these dual roles.

    • Justin D. Walter
    • Sille Remm
    • Markus A. Seeger
    News & Views
  • The central apparatus regulates the beating of motile cilia. High-resolution structures of the almost complete central apparatus are now reported in two separate studies, shedding light on the mechanism of ciliary beating and marking a new era in our molecular understanding of cilia architecture and function.

    • Elena A. Zehr
    • Antonina Roll-Mecak
    News & Views
  • The CRISPR–Cas enzyme Cas9 faces the challenge of identifying a specific nucleotide sequence within double-stranded DNA. New cryo-EM and biochemical studies show that in the earliest steps of binding, Cas9 bends the DNA and promotes unwinding of two base pairs, enabling it to efficiently scan the sequence of this critical region.

    • Selma Sinan
    • Rick Russell
    News & Views
  • Cryo-EM analysis reveals the mechanism by which chromatin is compacted at the centromere by the H3 histone variant CENP-N. Intriguingly, despite the structural differences between CENP-N and linker H1 histones, both appear to similarly compact higher-order nucleosome structures.

    • Katrina V. Good
    • Juan Ausió
    News & Views
  • Eukaryotes possess several clamp loaders comprising four common subunits and a fifth subunit unique to each complex. The RFC-A–E clamp loader loads the PCNA clamp at 3′-recessed structures for DNA replication. However, swapping a single subunit, Rad24, for RFC-A yields a clamp loader that prefers the 911 clamp and 5′-recessed DNA. Three new studies reveal detailed views of the clamp loading reaction and provide insights into substrate preferences of each loader.

    • David Jeruzalmi
    News & Views
  • The molecular mechanisms by which a few molecules of the long non-coding RNA Xist silence genes on the entire X chromosome are poorly understood. New evidence suggests that dimeric foci of Xist seed the formation of large protein assemblies that contain a wide spectrum of proteins, such as SPEN (SHARP), CIZ1, CELF, PTBP1 and components of Polycomb repressive complexes 1 and 2. These assemblies, each of which may contain hundreds to thousands of molecules of proteins, extend spatially beyond each focus of Xist, which explains how this long non-coding RNA triggers silencing across an entire chromosome.

    • Andrea Cerase
    • J. Mauro Calabrese
    • Gian Gaetano Tartaglia
    News & Views
  • The class II phosphatidylinositol 3-kinases (PI3Ks) serve important roles in diverse cellular processes. The lab of Volker Haucke has now determined high-resolution structures of mouse PI3KC2α in both active and inactive conformations, elucidating the autoregulatory mechanism of class II PI3K activation.

    • Pujuan Deng
    • Jun-Jie Gogo Liu
    News & Views
  • Growing evidence suggests that many ribosome-targeting antibiotics inhibit protein synthesis context specifically, which has important implications for drug development. New work reveals the structural basis of context-specific action of the classic translation inhibitor chloramphenicol and the oxazolidinones linezolid and radezolid.

    • Caillan Crowe-McAuliffe
    • Daniel N. Wilson
    News & Views