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.
Mariner transposition is a complex reaction that involves three DNA sites and six chemical reactions, which is carried out by a single transposase protein in a highly regulated and coordinated manner. Despite being the most widespread of all eukaryotic DNA transposons, key aspects of the mechanism have remained unclear, namely, the dynamics of the transpososome in which transposition takes place, and the number and role of individual subunits during the reaction. The studies in this manuscript demonstrate that the active site of a Mariner transposase sequentially cleaves two DNA strands of opposite polarity. In addition to providing a definitive answer to a long-standing question, their results identify a new mechanism that extends the catalytic repertoire of a vast and diverse family of nucleases based on the RNase H structural fold.
Deletion of subtelomeric homologous (SH) sequences from S. pombe had no effect on major cellular functions, but implicated subtelomeric sequences in a novel defense mechanism against telomere shortening. SH sequences prevented deleterious inter-chromosomal end fusion by facilitating intra-chromosomal circularization. The cells survive loss of telomeres and SH by inter- or intra-chromosomal end fusions, taking advantage of other highly similar DNA sequences around subtelomeres. Furthermore, subtelomeres play roles in blocking the spread of heterochromatin into neighboring regions, ensuring that the genes residing there are expressed. Protection of the subtelomeric borders is mediated by changes in chromatin modification that result exhibiting a nucleosome-free configuration that blocks spreading of silent heterochromatin into subtelomere-adjacent euchromatin regions. Thus, this work has uncovered the cryptic functions of subtelomeres in chromosome homeostasis and gene expression.
Analysis of in vitro evolution reveals the underlying distribution of catalytic activity among random sequences
While it is known that some RNA sequences are catalytic, the frequency of such sequences in a random pool is essentially uncharacterized. This article describes a quantitative view of how catalytic activity is distributed in a pool of random sequences. The rate constants of random sequences follow a log-normal distribution, suggesting an underlying mechanism for the emergence of catalytic activity as the product of many small contributions, common to many unrelated ribozymes. A quantitative understanding of the frequency of catalytic activity among random RNA sequences would be of broad interest, as knowing the probability that catalytic activities emerge is important for estimating the probability that self-reproducing molecules, leading to life itself, can emerge. The methods of converting evolutionary fitness into absolute rate constants and thereby determining the distribution of the original pool is of interest for those concerned with the in vitro evolution of ribozymes.