NAR’s Breakthrough Articles present high-impact studies answering long-standing questions in the field of nucleic acids research and/or opening up new areas and mechanistic hypotheses for investigation. These articles are chosen by the Editors on the recommendation of Editorial Board Members and Referees. Articles are accompanied by a brief synopsis explaining the findings of the paper and where they fit in the broader context of nucleic acids research. They represent the very best papers published at NAR.
Features of genomic organization in a nucleotide-resolution molecular model of the Escherichia coli chromosome
"The challenge that modeling a chromosome represents is substantial: the E. coli chromosome, for example, includes over 4.6 million base pairs (Mb) of DNA, with a contour length of 1.6 mm compressed into a cell less than 3 μm in length in a predictable orientation". In this study, the authors describe structural models of entire E. coli chromosomes at resolutions of one nucleotide per bead (1NTB) confined within the experimentally determined volume of the nucleoid. The study employs a novel multi-scale methodology that integrates a whole range of experimental data, and shows the central importance of transcription and supercoiling in bacterial chromosome structure.
This study reveals that a novel antibacterial toxin from Yersinia kristensenii shares a common structural fold with RNase A and possesses the superfamily's characteristic ribonuclease activity. Homologs of this toxin are associated with diverse secretion systems in both Gram-negative and Gram-positive bacteria, suggesting that RNase A-like toxins are commonly deployed in inter-bacterial competition. Contact-dependent growth inhibition (CDI) is a toxin-delivery platform that is distributed widely amongst proteobacteria and is particularly common in pathogens. There is substantial functional and structural diversity observed between CDI toxin/immunity protein pairs, and these systems are important mediators of inter-cellular competition and self/nonself recognition in bacteria. Antibacterial toxin secretion systems are ubiquitous in nature and are beginning to inspire the development of “next generation” antimicrobial therapies.
Telomeres are special structures at the ends of linear chromosomes. Maintenance of functional telomeres is essential for genome stability, and dysregulation of telomere synthesis is one of the hallmarks of cancer. Human telomeres consist of several kilobases of repeated DNA sequences, terminating in a 3’ single-strand Grich DNA overhang. The overhang is synthesized by telomerase, which is often regarded as the essential regulator of overhang length. Here, the laboratory of Carolyn M. Price laboratory reports that filling-in of the recessed, C-rich strand is as important as the for maintaining human telomere length as telomerase itself. They mutated CTC1, a subunit of a multiprotein complex that aids in synthesis of the C-rich strand. Loss of CTC1 leads to gradual telomere shortening, akin to what is observed in cells that lack telomerase. In the absence of CTC1, telomerase continues to extend the G-rich DNA overhang, but the elongated overhang cannot be converted to double-stranded D ...